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Sample records for immunity disease susceptibility

  1. Linking susceptibility to infectious diseases to immune system abnormalities among HIV Exposed Uninfected Infants

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    Candice Ruck

    2016-08-01

    Full Text Available HIV exposed, uninfected (HEU infants have been shown to have an increase in overall mortality from infectious causes when compared to HIV unexposed, uninfected (HU infants. This is the case in both resource-rich and resource-limited settings. We explore here the concept that specific types of infectious diseases that are more common among HEU infants could provide clues as to the potential underlying immunological abnormalities. The most commonly reported infections in HEU vs. HU are caused by encapsulated bacteria; this suggests the existence of a less effective humoral (antibody, complement immune response. Decreased transplacental transfer of protective maternal antibodies has been seen consistently among HEU newborns, suggesting that this may indeed be one of the key drivers of their susceptibility to infections with encapsulated bacteria. Reassuringly, HEU humoral response to vaccination appears to be well conserved. While there appears to be an increase in overall incidence of acute viral infections, no specific pattern of acute viral infections has emerged; and while there is evidence of increased chronic viral infection from perinatal transmission of hepatitis C and CMV, no data exist to suggest an increase in adverse outcomes. Thus, no firm conclusions about anti-viral effector mechanisms can be drawn. However, the most unusual of reported infections among the HEU have been opportunistic infections, suggesting the possibility of underlying defects in CD4 helper and overall immune regulatory function. This may relate to the observation that the immunological profile of HEUs indicate more activated T cell profile as well as a more inflammatory innate immune response. However, both of these observations appear temporary, marked in early infancy, but no longer evident later in life. The causes of these changes in early life immune profile are likely multifactorial and may be related to in utero exposure to HIV, but also to increased

  2. Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases.

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    Martínez, A; Varadé, J; Márquez, A; Cénit, M C; Espino, L; Perdigones, N; Santiago, J L; Fernández-Arquero, M; de la Calle, H; Arroyo, R; Mendoza, J L; Fernández-Gutiérrez, B; de la Concha, E G; Urcelay, E

    2008-09-01

    The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interleukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases. The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type 1 diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test. The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 x 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07-1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82-1.28). The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.

  3. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

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    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  4. Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease

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    Cristen Chafin

    2010-10-01

    Full Text Available Cristen Chafin2, Sarah Muse2, Raquel Hontecillas5, Josep Bassaganya-Riera5, David L Caudell2, Samuel K Shimp III4, M Nichole Rylander4, John Zhang6, Liwu Li3, Christopher M Reilly1,21Virginia College of Osteopathic Medicine, 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 3Department of Biological Sciences, 4Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 5Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 6Medical University of SC, Charleston, SC, USAAbstract: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-γ has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-γ gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM mouse model. PPAR-γ+/+ and PPAR-γ-/- mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-γ+/+ and PPAR-γ-/- mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-γ-/- mice were significantly more severe compared with the PPAR-γ+/+ animals. We observed that the PPAR-γ-/- mice had decreased CD4+CD25+ regulatory T cells and an increased CD8+:CD4+ ratio as compared with the PPAR-γ+/+ mice, suggesting that PPAR-γ has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-γ-/- mice at two weeks as compared with the PPAR-γ+/+ animals. Taken together, these studies show that

  5. India, Genomic diversity & Disease susceptibility

    Indian Academy of Sciences (India)

    Table of contents. India, Genomic diversity & Disease susceptibility · India, a paradise for Genetic Studies · Involved in earlier stages of Immune response protecting us from Diseases, Responsible for kidney and other transplant rejections Inherited from our parents · PowerPoint Presentation · Slide 5 · Slide 6 · Slide 7.

  6. The gene-immune-behavioral pathway: Gamma-interferon (IFN-γ) simultaneously coordinates susceptibility to infectious disease and harm avoidance behaviors.

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    MacMurray, James; Comings, David E; Napolioni, Valerio

    2014-01-01

    Cytokine gene variants are known to influence both infectious disease susceptibility and harm-avoidant behaviors, suggesting that these risk variants may be pleiotropically linked to instinctual disease-avoidant traits. The gamma-interferon (IFNG) +874 T>A polymorphism (rs2430561) is an ideal candidate gene variant for immune-behavioral studies. It is a functional SNP, regulating IFNG mRNA expression; it is known to modulate serotonergic activity and is therefore capable of modifying behavior; and it has previously been associated with increased susceptibility to malaria, tuberculosis, leprosy and Chagas disease. We hypothesized that the infectious disease-high-risk IFNG +874 A-allele would be associated with four personality traits previously reported as behavioral defenses against infection: Harm Avoidance (HA), Extraversion (E), Exploratory Excitability (Exp E), and Openness to Experience (O). We tested this hypothesis in a sample of 168 healthy university students from Southern California genotyped for IFNG +874 T>A and evaluated by the Temperament and Character Inventory-Revised (TCI-R) and the NEO Five-Factor Inventory (NEO-FFI). We found that the infectious disease-high-risk IFNG +874 A-allele was associated with increased HA (P=0.001) and decreased E (P=0.030) and Exp E (P=0.030). These findings suggest that the IFNG +874 A gene variant is linked both to infectious disease susceptibility and to proactive behavioral defenses that reduce infection risk in healthy subjects. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. DEVELOPMENT OF A RISK ASSESSMENT MODEL FOR THE EFFECTS OF ORGANOPHOSPHORUS PESTICIDES ON INFECTIOUS DISEASE SUSCEPTIBILITY AND THE IMMUNE SYSTEM

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    There is increased concern about the sublethal effects of organophosphorus (OP) pesticides on human and animal health. This class of chemicals has been shown to affect the immune function of macrophages and lymphocytes. Malathion, an OP compound, is one of the most widely used ...

  8. CISH and Susceptibility to Infectious Diseases

    OpenAIRE

    Khor, CC; Vannberg, FO; Chapman, SJ; Guo, H; Wong, SH; Walley, AJ; Vukcevic, D; Rautanen, A; Mills, TC; Chang, K-C; Kam, K-M; Crampin, AC; Ngwira, B; Leung, C-C; Tam, C-M

    2010-01-01

    BACKGROUND The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling. METHODS Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya,...

  9. CISH and susceptibility to infectious diseases.

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    Khor, Chiea C; Vannberg, Fredrik O; Chapman, Stephen J; Guo, Haiyan; Wong, Sunny H; Walley, Andrew J; Vukcevic, Damjan; Rautanen, Anna; Mills, Tara C; Chang, Kwok-Chiu; Kam, Kai-Man; Crampin, Amelia C; Ngwira, Bagrey; Leung, Chi-Chiu; Tam, Cheuk-Ming; Chan, Chiu-Yeung; Sung, Joseph J Y; Yew, Wing-Wai; Toh, Kai-Yee; Tay, Stacey K H; Kwiatkowski, Dominic; Lienhardt, Christian; Hien, Tran-Tinh; Day, Nicholas P; Peshu, Nobert; Marsh, Kevin; Maitland, Kathryn; Scott, J Anthony; Williams, Thomas N; Berkley, James A; Floyd, Sian; Tang, Nelson L S; Fine, Paul E M; Goh, Denise L M; Hill, Adrian V S

    2010-06-03

    The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling. Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections. We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P=3.8x10(-11) for all comparisons), with -292 accounting for most of the association signal (P=4.58x10(-7)). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production--that is, 25 to 40% less CISH expression. Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles. 2010 Massachusetts Medical Society

  10. CISH and Susceptibility to Infectious Diseases

    Science.gov (United States)

    Khor, Chiea C.; Vannberg, Fredrik O.; Chapman, Stephen J.; Guo, Haiyan; Wong, Sunny H.; Walley, Andrew J.; Vukcevic, Damjan; Rautanen, Anna; Mills, Tara C.; Chang, Kwok-Chiu; Kam, Kai-Man; Crampin, Amelia C.; Ngwira, Bagrey; Leung, Chi-Chiu; Tam, Cheuk-Ming; Chan, Chiu-Yeung; Sung, Joseph J.Y.; Yew, Wing-Wai; Toh, Kai-Yee; Tay, Stacey K.H.; Kwiatkowski, Dominic; Lienhardt, Christian; Hien, Tran-Tinh; Day, Nicholas P.; Peshu, Nobert; Marsh, Kevin; Maitland, Kathryn; Scott, J. Anthony; Williams, Thomas N.; Berkley, James A.; Floyd, Sian; Tang, Nelson L.S.; Fine, Paul E.M.; Goh, Denise L.M.; Hill, Adrian V.S.

    2013-01-01

    Background The interleukin-2 (IL2)-mediated immune response is critical for host defence against infectious pathogens. CISH, a suppressor of cytokine signalling, controls IL2 signalling. Methods We tested for association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis and severe malaria) in 8402 persons from the Gambia, Hong Kong, Kenya, Malawi, and Vietnam using a case-control design. We have previously tested twenty other immune-related genes in one or more of these sample collections. Results We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five SNPs (CISH −639, −292, −163, +1320 and +3415) within the CISH-associated locus were considered together in a multi-SNP score, we found substantial support for an effect of CISH genetic variants on susceptibility to bacteremia, malaria, and tuberculosis (overall P=3.8 × 10−11) with CISH −292 being “responsible” for the majority of the association signal (P=4.58×10−7). Peripheral blood mononuclear cells of adult volunteers carrying the CISH −292 variant showed a muted response to IL2 stimulation — in the form of 25-40% less CISH — when compared with “control” cells lacking the −292 variant. Conclusions Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signalling may play a major role in immunity against various infectious diseases. The overall risk of having one of these infectious diseases was found to be increased by at least 18 percent in individuals carrying the variant CISH alleles. PMID:20484391

  11. Mammary gland immunity and mastitis susceptibility.

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    Sordillo, Lorraine M; Streicher, Katie L

    2002-04-01

    Lactation is considered the final phase of the mammalian reproductive cycle, and the mammary gland provides milk for nourishment and disease resistance to the newborn. However, the cellular and soluble immune components associated with mammary tissues and secretion also can play an important role in protecting the gland from infectious diseases, such as mastitis. Mastitis can affect essentially all lactating mammals, but is especially problematic for dairy cattle. The most recent estimates from the National Mastitis Council suggest that mastitis affects one third of all dairy cows and will cost the dairy industry over 2 billion dollars annually in the United States in lost profits (National Mastitis Council (1996) Current Concepts in Bovine Mastitis, National Mastitis Council, Madison, WI). The overall impact of mastitis on the quality and quantity of milk produced for human consumption has provided the impetus to better understand the pathophysiology of the mammary gland and develop ways to enhance disease resistance through immunoregulation. As such, the bovine species has played a critical and prominent role in our current understanding of mammary gland immunobiology. This paper provides a comprehensive overview of mammary gland immunity and how the stage of lactation can impact important host defenses While this review emphasizes the bovine system, comparisons to humans and other domestic mammals will be addressed as well.

  12. Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.

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    Juliane Bremer

    Full Text Available The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

  13. Schistosoma mansoni; relationship between membrane turnover rates and susceptibility to immune damage. Part of a coordinated programme on preparation of irradiated vaccines against some human diseases

    International Nuclear Information System (INIS)

    Pereira Tavares, C.A.

    1983-11-01

    It is known that the schistosomulum of Schistosoma mansoni become refractory to damage by antibody and complement in vitro in the presence of serum, or Concanavalin A (Con A), or after contact with host tissues, presumably due to intrinsic changes in the surface membrane. This project studied the effect of dialysed fetal calf serum (DFCS) and Con A on the synthesis and turnover of individual proteins in the surface membrane using the incorporation of 14 C- and 3 H-labelled Arginine and the separation of the membrane proteins in SDS-PAGE. The results indicate that during the period in which schistosomules become resistant to immune attack, no qualitative alterations in electrophoretic patterns of surface proteins were observed. There was, however, a marked heterogeneity in synthesis and degradation among constituent proteins. In addition, Con A which had been shown to be effective in stimulating loss of susceptibility to immune attack, caused a slight decrease in the synthesis and turnover rate of high molecular weight proteins, whilst DFCS increased synthesis and turnover of low molecular weight proteins. This suggests that at least two processes occur in the membrane which may be related to the development of protection against immune attack. Serum might stimulate the loss of crucial antigens by accelerating their turnover making antibody attachment difficult, and Con A could be stabilizing the membrane by crosslinking large macromolecules. It is possible that in vivo both mechanisms occur to make the schistosomule surface refractory to damage

  14. Altered IFN-γ-mediated immunity and transcriptional expression patterns in N-Ethyl-N-nitrosourea-induced STAT4 mutants confer susceptibility to acute typhoid-like disease.

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    Eva, Megan M; Yuki, Kyoko E; Dauphinee, Shauna M; Schwartzentruber, Jeremy A; Pyzik, Michal; Paquet, Marilène; Lathrop, Mark; Majewski, Jacek; Vidal, Silvia M; Malo, Danielle

    2014-01-01

    Salmonella enterica is a ubiquitous Gram-negative intracellular bacterium that continues to pose a global challenge to human health. The etiology of Salmonella pathogenesis is complex and controlled by pathogen, environmental, and host genetic factors. In fact, patients immunodeficient in genes in the IL-12, IL-23/IFN-γ pathway are predisposed to invasive nontyphoidal Salmonella infection. Using a forward genomics approach by N-ethyl-N-nitrosourea (ENU) germline mutagenesis in mice, we identified the Ity14 (Immunity to Typhimurium locus 14) pedigree exhibiting increased susceptibility following in vivo Salmonella challenge. A DNA-binding domain mutation (p.G418_E445) in Stat4 (Signal Transducer and Activator of Transcription Factor 4) was the causative mutation. STAT4 signals downstream of IL-12 to mediate transcriptional regulation of inflammatory immune responses. In mutant Ity14 mice, the increased splenic and hepatic bacterial load resulted from an intrinsic defect in innate cell function, IFN-γ-mediated immunity, and disorganized granuloma formation. We further show that NK and NKT cells play an important role in mediating control of Salmonella in Stat4(Ity14/Ity14) mice. Stat4(Ity14/Ity14) mice had increased expression of genes involved in cell-cell interactions and communication, as well as increased CD11b expression on a subset of splenic myeloid dendritic cells, resulting in compromised recruitment of inflammatory cells to the spleen during Salmonella infection. Stat4(Ity14/Ity14) presented upregulated compensatory mechanisms, although inefficient and ultimately Stat4(Ity14/Ity14) mice develop fatal bacteremia. The following study further elucidates the pathophysiological impact of STAT4 during Salmonella infection.

  15. Genetic susceptibility to Grave's disease.

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    Li, Hong; Chen, Qiuying

    2013-06-01

    The variety of clinical presentations of eye changes in patients with Graves' disease (GD) suggests that complex interactions between genetic, environmental, endogenous and local factors influence the severity of Graves' ophthalmopathy (GO). It is thought that the development of GO might be influenced by genetic factors and environmental factors, such as cigarette smoking. At present, however, the role of genetic factors in the development of GO is not known. On the basis of studies with candidate genes and other genetic approaches, several susceptibility loci in GO have been proposed, including immunological genes, human leukocyte antigen (HLA), cytotoxic T-lymphocyte antigen-4 (CTLA-4), regulatory T-cell genes and thyroid-specific genes. This review gives a brief overview of the current range of major susceptibility genes found for GD.

  16. Immunity to community: what can immune pathways tell us about disease patterns in corals?

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    Mydlarz, L. D.; Fuess, L.; Pinzon, J. C.; Weil, E.

    2016-02-01

    Predicting species composition and abundances is one of the most fundamental questions in ecology. This question is even more pressing in marine ecology and coral reefs since communities are changing at a rapid pace due to climate-related changes. Increases in disease prevalence and severity are just some of the consequences of these environmental changes. Particularly in coral reef ecosystems, diseases are increasing and driving region-wide population collapses. It has become clear, however, that not all reefs or coral species are affected by disease equally. In fact, the Caribbean is a concentrated area for diseases. The patterns in which disease manifests itself on an individual reef are also proving interesting, as not all coral species are affected by disease equally. Some species are host to different diseases, but seem to successfully fight them reducing mortality. Other species are disproportionately infected on any given reef and experience high mortality due to disease. We are interested in the role immunity can play in directing these patterns and are evaluating coral immunity using several novel approaches. We exposed 4 species of corals with different disease susceptibilities to immune stimulators and quantified of coral immunity using a combination of full transcriptome sequencing and protein activity assays for gene to phenotype analysis. We also mapped gene expression changes onto immune pathways (i.e. melanin-cascade, antimicrobial peptide synthesis, complement cascade, lectin-opsonization) to evaluate expression of immune pathways between species. In our preliminary data we found many immune genes in the disease susceptible Orbicella faveolata underwent changes in gene expression opposite of the predictions and may disply `dysfunctional' patterns of expression. We will present expression data for 4 species of coral and assess how these transcriptional and protein immune responses are related to disease susceptibility in nature, thus scaling up

  17. Endocrine Disrupting Chemicals and Disease Susceptibility

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    Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

    2011-01-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

  18. Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

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    Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

    2015-04-01

    Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

  19. Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Albor Dobón

    2015-04-01

    Full Text Available Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

  20. Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

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    Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

    2013-01-01

    , when a subclinical, mild thyroiditis was induced with soluble mTg and low doses of interleukin-1, to simulate pre-existing autoimmunity in patients subjected to cancer immunotherapy, mononuclear infiltration into the thyroid was enhanced. Conclusions: Our current findings indicate that genetic predisposition to autoimmune disease could enhance autoimmunity during induction of tumor immunity in thyroiditis-susceptible mice. Thus, HLA genotyping of cancer patients should be part of any risk assessment. PMID:23777580

  1. A comparison of disease susceptibility and innate immune response between diploid and triploid Atlantic salmon (Salmo salar) siblings following experimental infection with Neoparamoeba perurans, causative agent of amoebic gill disease.

    Science.gov (United States)

    Chalmers, Lynn; Taylor, John F; Roy, William; Preston, Andrew C; Migaud, Herve; Adams, Alexandra

    2017-08-01

    Few studies have focussed on the health and immunity of triploid Atlantic salmon and therefore much is still unknown about their response to commercially significant pathogens. This is important if triploid stocks are to be considered for full-scale commercial production. This study aimed to investigate and compare the response of triploid and diploid Atlantic salmon to an experimental challenge with Neoparamoeba perurans, causative agent of amoebic gill disease (AGD). This disease is economically significant for the aquaculture industry. The results indicated that ploidy had no significant effect on gross gill score or gill filaments affected, while infection and time had significant effects. Ploidy, infection and time did not affect complement or anti-protease activities. Ploidy had a significant effect on lysozyme activity at 21 days post-infection (while infection and time did not), although activity was within the ranges previously recorded for salmonids. Stock did not significantly affect any of the parameters measured. Based on the study results, it can be suggested that ploidy does not affect the manifestation or severity of AGD pathology or the serum innate immune response. Additionally, the serum immune response of diploid and triploid Atlantic salmon may not be significantly affected by amoebic gill disease.

  2. Homeostasis, inflammation, and disease susceptibility.

    Science.gov (United States)

    Kotas, Maya E; Medzhitov, Ruslan

    2015-02-26

    While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Quantitative Susceptibility Mapping in Parkinson's Disease.

    Science.gov (United States)

    Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

    2016-01-01

    Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

  4. Host susceptibility hypothesis for shell disease in American lobsters.

    Science.gov (United States)

    Tlusty, Michael F; Smolowitz, Roxanna M; Halvorson, Harlyn O; DeVito, Simone E

    2007-12-01

    Epizootic shell disease (ESD) in American lobsters Homarus americanus is the bacterial degradation of the carapace resulting in extensive irregular, deep erosions. The disease is having a major impact on the health and mortality of some American lobster populations, and its effects are being transferred to the economics of the fishery. While the onset and progression of ESD in American lobsters is undoubtedly multifactorial, there is little understanding of the direct causality of this disease. The host susceptibility hypothesis developed here states that although numerous environmental and pathological factors may vary around a lobster, it is eventually the lobster's internal state that is permissive to or shields it from the final onset of the diseased state. To support the host susceptibility hypothesis, we conceptualized a model of shell disease onset and severity to allow further research on shell disease to progress from a structured model. The model states that shell disease onset will occur when the net cuticle degradation (bacterial degradation, decrease of host immune response to bacteria, natural wear, and resorption) is greater than the net deposition (growth, maintenance, and inflammatory response) of the shell. Furthermore, lesion severity depends on the extent to which cuticle degradation exceeds deposition. This model is consistent with natural observations of shell disease in American lobster.

  5. Genetics and genomics of susceptibility and immune response to necrotic enteritis in chicken: a review.

    Science.gov (United States)

    Zahoor, Imran; Ghayas, Abdul; Basheer, Atia

    2018-02-01

    Global poultry production is facing many challenges and is currently under pressure due to the presence of several diseases like Necrotic Enteritis (NE). It is estimated that NE-caused global economic losses has increased from 2 billion to 6 billion US$ in 2015 because it is not easy to diagnose and control disease at the earlier stage of occurrence. Additionally, ban on the in-feed antibiotics and some other genetic and non-genetic predisposing factors affect the occurrence of the disease. Though the incidence of the disease can be reduced by minimizing the predisposing factors and through immunization of birds but there is no single remedy to control the disease. Therefore, we suggest that there is need to find out the genetic variants that could help to select the birds resistant to NE. The current review details the pertinent features about the genetic and genomics of susceptibility and immune response of birds to Necrotic Enteritis. We report here the list of candidate gene reported for their involvement with the susceptibility and/or resistance to the disease. However, most of these genes are involved in immune-related functions. For better understanding of the role of Clostridium perfringens and its toxins in the pathogenesis of disease there is need to unveil the association between any specific genetic variation and clinical status of NE. However, the presence of substantial genetic variations among different breeds/strains of chicken shows that it is possible to develop broiler strain with genetic resistant against NE. It would help in the cost-effective and sustainable production of safe broiler meat.

  6. Therapeutic potential of helminths in autoimmune diseases: helminth-derived immune-regulators and immune balance.

    Science.gov (United States)

    Wang, Meng; Wu, Linxiang; Weng, Rennan; Zheng, Weihong; Wu, Zhongdao; Lv, Zhiyue

    2017-08-01

    Helminths have accompanied human throughout history by releasing immune-evasion molecules that could counteract an aberrant immune response within the host. In the past decades, helminth infections are becoming less prevalent possibly due to the developed sanitation. Meanwhile, the incidence of autoimmune diseases is increasing, which cannot be exclusively explained by the changes of susceptibility genes. While the hygiene hypothesis casts light on the problem. The infections of helminths are believed to interact with and regulate human immunity with the byproduct of suppressing the autoimmune diseases. Thus, helminths are potential to treat or cure the autoimmune diseases. The therapeutic progresses and possible immune suppression mechanisms are illustrated in the review. The helminths that are studied most intensively include Heligmosomoides polygyrus, Hymenolepis diminuta, Schistosoma mansoni, Trichinella spiralis, and Trichuris suis. Special attentions are paid on the booming animal models and clinical trials that are to detect the efficiency of immune-modulating helminth-derived molecules on autoimmune diseases. These trials provide us with a prosperous clinical perspective, but the precise mechanism of the down-regulatory immune response remains to be clarified. More efforts are needed to be dedicated until these parasite-derived immune modulators could be used in clinic to treat or cure the autoimmune diseases under a standard management.

  7. Interferon Lambda: Modulating Immunity in Infectious Diseases.

    Science.gov (United States)

    Syedbasha, Mohammedyaseen; Egli, Adrian

    2017-01-01

    Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis . Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage

  8. Pregnancy and Susceptibility to Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Elisabeth Sappenfield

    2013-01-01

    Full Text Available To summarize the literature regarding susceptibility of pregnant women to infectious diseases and severity of resulting disease, we conducted a review using a PubMed search and other strategies. Studies were included if they reported information on infection risk or disease outcome in pregnant women. In all, 1454 abstracts were reviewed, and a total of 85 studies were included. Data were extracted regarding number of cases in pregnant women, rates of infection, risk factors for disease severity or complications, and maternal outcomes. The evidence indicates that pregnancy is associated with increased severity of some infectious diseases, such as influenza, malaria, hepatitis E, and herpes simplex virus (HSV infection (risk for dissemination/hepatitis; there is also some evidence for increased severity of measles and smallpox. Disease severity seems higher with advanced pregnancy. Pregnant women may be more susceptible to acquisition of malaria, HIV infection, and listeriosis, although the evidence is limited. These results reinforce the importance of infection prevention as well as of early identification and treatment of suspected influenza, malaria, hepatitis E, and HSV disease during pregnancy.

  9. Natural evolution, disease, and localization in the immune system

    Science.gov (United States)

    Deem, Michael

    2004-03-01

    Adaptive vertebrate immune system is a wonder of modern evolution. Under most circumstances, the dynamics of the immune system is well-matched to the dynamics of pathogen growth during a typical infection. Some pathogens, however, have evolved escape mechanisms that interact in subtle ways with the immune system dynamics. In addition, negative interactions the immune system, which has evolved over 400 000 000 years, and vaccination,which has been practiced for only 200 years, are possible. For example,vaccination against the flu can actually increase susceptibility to the flu in the next year. As another example, vaccination against one of the four strains of dengue fever typically increases susceptibility against the other three strains. Immunodominance also arises in the immune system control of nascent tumors--the immune system recognizes only a small subset of the tumor specific antigens, and the rest are free to grow and cause tumor growth. In this talk, I present a physical theory of original antigenic sin and immunodominance. How localization in the immune system leads to the observed phenomena is discussed. 1) M. W. Deem and H. Y. Lee, ``Sequence Space Localization in the Immune System Response to Vaccination and Disease,'' Phys. Rev. Lett. 91 (2003) 068101

  10. Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice.

    Science.gov (United States)

    Taylor, Andrew K; Cao, Weiping; Vora, Keyur P; De La Cruz, Juan; Shieh, Wun-Ju; Zaki, Sherif R; Katz, Jacqueline M; Sambhara, Suryaprakash; Gangappa, Shivaprakash

    2013-02-01

    Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

  11. PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility

    Directory of Open Access Journals (Sweden)

    Pradhan V

    2010-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype autoimmune disease. SLE is a result of one or more immune mechanisms, like autoantibody production, complement activation, multiple inflammation and immune complex deposition leading to organ tissue damage. SLE affected patients are susceptible to common and opportunistic infections. There are several reports suggesting that Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Genetic factors and environmental factors also play an important role in the overall susceptibility to SLE pathophysiology. Recently, protein tyrosine phosphatase, non-receptor type 22 (PTPN22 gene, has been found to be associated with several autoimmune diseases like SLE, Grave′s disease and Hashimoto thyroiditis. The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp has been associated with autoimmune diseases. The PTPN22 locus is also found to be responsible for development of pulmonary tuberculosis in certain populations. The PTPN22 1858C/T gene locus will be ideal to look for SLE susceptibility to tuberculosis in the Indian population. In this review, we focus on human PTPN22 gene structure and function as well as the association of PTPN22 gene polymorphisms with SLE susceptibility

  12. [Emotional stress-induced Shanghuo syndrome increases disease susceptibility].

    Science.gov (United States)

    Zhu, Si-Rui; Luo, Xiang; Li, Yi-Fang; Hiroshi, Kurihara; He, Rong-Rong

    2018-04-01

    Shanghuo(excessive internal heat) is a special organic state based on the concept of traditional Chinese medicine(TCM), commonly known as the abnormal heating syndrome of body in folks. With the acceleration of modern life rhythm and the increase of the social competition pressure, emotional stress has become an important cause for the spread of Shanghuo symptoms. What's more, Shanghuo can impact the body physiological functions to cause the onset, recurrence and progression of common diseases, harming the health of the body. According to the long-term research findings, the author found that Shanghuo referred to the imbalance of multiple physiological functions, such as nerve, immunity and metabolism, caused by emotional stress. "Shanghuo" is not a disease itself, but it can increase the susceptibility to a variety of diseases. This study reviewed the traditional medicine theory and the modern medical studies, and explored the relevance and correlation mechanisms between the Shanghuo symptoms and disease susceptibility, so as to provide a reference to improve the state of sub-health and prevent or treat modern diseases. Copyright© by the Chinese Pharmaceutical Association.

  13. A Strong Immune Response in Young Adult Honeybees Masks Their Increased Susceptibility to Infection Compared to Older Bees

    Science.gov (United States)

    Bull, James C.; Ryabov, Eugene V.; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A.; Pell, Judith K.; Osborne, Juliet L.; Chandler, Dave

    2012-01-01

    Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance (“housekeeping”) tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger “house” bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease

  14. Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Onengut, Suna; Chen, Wei-Min

    2015-01-01

    Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array...... and tested for association with seven disease-specific autoantibodies in a large cross-sectional cohort of 6,160 type 1 diabetes-affected siblings. The genetic association with positivity for GAD autoantibodies (GADAs), IA2 antigen (IA-2A), zinc transporter 8, thyroid peroxidase, gastric parietal cells (PCAs...... and constitute candidates for early screening. Major susceptibility loci for islet autoantibodies are separate from type 1 diabetes risk, which may have consequences for intervention strategies to reduce autoimmunity....

  15. Role of T cell receptor delta gene in susceptibility to celiac disease.

    Science.gov (United States)

    Roschmann, E; Wienker, T F; Volk, B A

    1996-02-01

    There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

  16. Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.

    Science.gov (United States)

    Nilsson, Eric E; Skinner, Michael K

    2015-01-01

    Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Cancer as an immune-mediated disease

    Directory of Open Access Journals (Sweden)

    Shurin MR

    2012-06-01

    Full Text Available Michael R ShurinDepartments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: The link between oncology and immunology has a long history and its development is forced by the necessity to develop innovative and highly efficient modalities for immunological destruction of malignant cells. The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, as these treatments do not eliminate all cancerous cells, do not address the immunosuppressive nature of the disease and can further impair the patient's immune response weakening patient's resistance to the cancer. Multidisciplinary analysis of the interaction between the immune system and cancer in preclinical and clinical settings suggests that the immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of malfunctions in immunity, as malignant cells manage to escape recognition and elimination by the immune system. Chronic infections and inflammation associated with limited or polarized immune responses also contribute to carcinogenesis and tumor progression. The tumor immunoenvironment represents specific conditions and elements that support cancerous cell survival, proliferation and spreading. On the other hand, the specificity and strength of antitumor immunity is a powerful and efficient tool that can be used to recognize and destroy neoplastic cells or their supporting microenvironment. Understanding the role of the immune system in controlling and supporting tumor initiation, formation, growth and progression has crucial implications for cancer therapy and will therefore guide the future development of cancer immunotherapy and its combination with conventional therapies to achieve optimal antitumor effects in patients with different types of cancer.Keywords: tumor immunology and immunotherapy, tumor immunoenvironment, cancer, immunosuppression

  18. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

    Science.gov (United States)

    Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

    2015-04-09

    Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children

    DEFF Research Database (Denmark)

    Lundbo, Lene Fogt; Harboe, Zitta Barrella; Clausen, Louise Nygaard

    2014-01-01

    BACKGROUND: Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2......, on susceptibility and disease severity of IPD in previously healthy children aged

  20. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  1. Skin immune sentinels in health and disease.

    Science.gov (United States)

    Nestle, Frank O; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J

    2009-10-01

    Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.

  2. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  3. Susceptibility based upon Chemical Interaction with Disease ...

    Science.gov (United States)

    One of the challenges facing toxicology and risk assessment is that numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest is the potential for chemicals to interact with background aging and disease processes, an interaction that may yield cumulative damage, altered chemical potency, and increased disease incidence. This review outlines the interactions possible between chemicals and background disease and identifies the type of information needed to evaluate such interactions. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which allows the identification of vulnerable individuals based upon the level of risk biomarker. The impact of toxic chemicals on this biomarker can then be used to predict how the chemical modifies disease risk as long as related mechanistic and toxicological data are consistent with toxicant effect on the disease process. Several case studies are briefly presented which describe the toxic chemical, the clinical biomarker and the impacted disease including: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration rate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; trichloroethylene/increased anti-nuclear antibody/autoimmunity; dioxin/increased CYP1A1/hypertension. These case studies point o

  4. Distinctive cellular immunity in genetically susceptible BALB/c mice recovered from Leishmania major infection or after subcutaneous immunization with killed parasites

    International Nuclear Information System (INIS)

    Liew, F.Y.; Dhaliwal, J.S.

    1987-01-01

    Genetically susceptible BALB/c mice are refractory to further infection after recovery from Leishmania major infection after a sublethal dose of gamma-irradiation. In contrast, mice immunized with killed promastigotes s.c. develop exacerbated lesions after infection. Both groups of mice produce only a low level of specific antibody and no detectable cytotoxic T cells, but do have a strong antigen-specific DTH, which is adoptively transferable with Lyt-1+2-, L3T4+ T cells. Kinetic and histological studies revealed that mice immunized s.c. developed Jones-Mote hypersensitivity, peaking at 15 hr. with little mononuclear cell infiltration at the site of antigen administration; whereas mice that had recovered from infection developed tuberculin-type of reactivity, peaking at 24 to 48 hr, with intense mononuclear cell infiltration. Splenic T cells from recovered mice, when injected into the footpads of normal recipients together with live promastigotes, were able to retard lesion development; whereas T cells from s.c. immunized mice, when similarly transferred, accelerated disease progression. Antigen-specific culture supernatant of spleen cells from recovered mice also activated normal resident peritoneal macrophages to kill intracellular L. major amastigotes and tumor cells. Culture supernatants of spleen cells from s.c. immunized or normal mice were devoid of such activities. Part of the macrophage-activating potential can be inhibited by antibody specific for IFN-gamma. These results therefore demonstrate that whereas the Jones-Mote reaction is correlated with disease exacerbation, the tuberculin-type of DTH may be protective. Furthermore, in vivo immunity is directly related to the capacity of T cells to produce macrophage-activating factor

  5. Susceptibility to infection and immune response in insular and continental populations of Egyptian vulture: implications for conservation.

    Directory of Open Access Journals (Sweden)

    Laura Gangoso

    Full Text Available BACKGROUND: A generalized decline in populations of Old World avian scavengers is occurring on a global scale. The main cause of the observed crisis in continental populations of these birds should be looked for in the interaction between two factors -- changes in livestock management, including the increased use of pharmaceutical products, and disease. Insular vertebrates seem to be especially susceptible to diseases induced by the arrival of exotic pathogens, a process often favored by human activities, and sedentary and highly dense insular scavengers populations may be thus especially exposed to infection by such pathogens. Here, we compare pathogen prevalence and immune response in insular and continental populations of the globally endangered Egyptian vulture under similar livestock management scenarios, but with different ecological and evolutionary perspectives. METHODS/PRINCIPAL FINDINGS: Adult, immature, and fledgling vultures from the Canary Islands and the Iberian Peninsula were sampled to determine a the prevalence of seven pathogen taxa and b their immunocompetence, as measured by monitoring techniques (white blood cells counts and immunoglobulins. In the Canarian population, pathogen prevalence was higher and, in addition, an association among pathogens was apparent, contrary to the situation detected in continental populations. Despite that, insular fledglings showed lower leukocyte profiles than continental birds and Canarian fledglings infected by Chlamydophila psittaci showed poorer cellular immune response. CONCLUSIONS/SIGNIFICANCE: A combination of environmental and ecological factors may contribute to explain the high susceptibility to infection found in insular vultures. The scenario described here may be similar in other insular systems where populations of carrion-eaters are in strong decline and are seriously threatened. Higher susceptibility to infection may be a further factor contributing decisively to the extinction

  6. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

    Science.gov (United States)

    Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

    2016-03-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. The role of the immune system in kidney disease.

    Science.gov (United States)

    Tecklenborg, J; Clayton, D; Siebert, S; Coley, S M

    2018-05-01

    The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. © 2018 British Society for Immunology.

  8. Differential susceptibility of HIV strains to innate immune factors in human cervical-vaginal secretions

    Directory of Open Access Journals (Sweden)

    Mimi Ghosh

    2010-07-01

    Full Text Available Mimi Ghosh, John V Fahey, Charles R WiraDepartment of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire, USAAbstract: The female reproductive tract (FRT is protected by innate and adaptive immune mechanisms, which work in concert to defend against human immunodeficiency virus (HIV and other sexually transmitted infections (STIs. Under the control of sex hormones throughout a woman’s life, the immune system in the FRT has evolved to meet the challenges of protection against STIs, coupled with the need to sustain the development of new life. The studies presented in this review focus on the threat of HIV infection and the levels of protection present in the FRT during the menstrual cycle. Studies from our laboratory and others, examined the presence and variability of immune components against viral infection in the FRT. Our findings indicate that there are some factors in the FRT secretions that inhibit and enhance infectivity of individual strains of HIV. Given the complexities of hormonal regulation, identification of the elements involved in susceptibility to and protection against HIV in women must involve a careful analysis of transmitted viruses and a clear understanding of immune protection in the FRT.Keywords: HIV susceptibility, CVL

  9. Chemical modulators of the innate immune response alter gypsy moth larval susceptibility to Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    Broderick Nichole A

    2010-04-01

    Full Text Available Abstract Background The gut comprises an essential barrier that protects both invertebrate and vertebrate animals from invasion by microorganisms. Disruption of the balanced relationship between indigenous gut microbiota and their host can result in gut bacteria eliciting host responses similar to those caused by invasive pathogens. For example, ingestion of Bacillus thuringiensis by larvae of some species of susceptible Lepidoptera can result in normally benign enteric bacteria exerting pathogenic effects. Results We explored the potential role of the insect immune response in mortality caused by B. thuringiensis in conjunction with gut bacteria. Two lines of evidence support such a role. First, ingestion of B. thuringiensis by gypsy moth larvae led to the depletion of their hemocytes. Second, pharmacological agents that are known to modulate innate immune responses of invertebrates and vertebrates altered larval mortality induced by B. thuringiensis. Specifically, Gram-negative peptidoglycan pre-treated with lysozyme accelerated B. thuringiensis-induced killing of larvae previously made less susceptible due to treatment with antibiotics. Conversely, several inhibitors of the innate immune response (eicosanoid inhibitors and antioxidants increased the host's survival time following ingestion of B. thuringiensis. Conclusions This study demonstrates that B. thuringiensis infection provokes changes in the cellular immune response of gypsy moth larvae. The effects of chemicals known to modulate the innate immune response of many invertebrates and vertebrates, including Lepidoptera, also indicate a role of this response in B. thuringiensis killing. Interactions among B. thuringiensis toxin, enteric bacteria, and aspects of the gypsy moth immune response may provide a novel model to decipher mechanisms of sepsis associated with bacteria of gut origin.

  10. Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation.

    Science.gov (United States)

    Mehta, Minesh; Ahmed, Shifat; Dryden, Gerald

    2017-08-01

    Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

  11. Immune-mediated diseases and microbial exposure in early life

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...

  12. Infectious Diseases and Immunizations in International Adoption.

    Science.gov (United States)

    Obringer, Emily; Walsh, Linda

    2017-02-01

    Children who are adopted internationally have an increased risk of infectious diseases due to endemic conditions and variable access to preventive health care, such as vaccines, in their country of origin. Pediatricians and other providers who care for children should be familiar with the recommended screening for newly arrived international adoptees. Testing for gastrointestinal pathogens, tuberculosis, hepatitis, syphilis, and HIV should be routinely performed. Other endemic diseases and common skin infections may need to be assessed. Evaluation of the child's immunization record is also important, as nearly all international adoptees will require catch-up vaccines. The provider may also be asked to review medical records prior to adoption, provide travel advice, and ensure that parents and other close contacts are up-to-date on immunizations prior to the arrival of the newest family member. The pediatrician serves a unique role in facilitating the evaluation, treatment, and prevention of infectious diseases in international adoptees. [Pediatr Ann. 2017;46(2):e56-e60.]. Copyright 2017, SLACK Incorporated.

  13. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  14. Immunization history of children with inflammatory bowel disease.

    Science.gov (United States)

    Soon, Ing Shian; deBruyn, Jennifer C C; Wrobel, Iwona

    2013-04-01

    Protection against vaccine-preventable diseases is important in children with inflammatory bowel disease (IBD) due to frequent immunosuppressive therapy use. The chronic relapsing nature and treatment regimen of IBD may necessitate modified timing of immunizations. To evaluate the completeness of immunizations in children with IBD. Immunization records of all children with IBD followed at the Alberta Children's Hospital (Calgary, Alberta) were reviewed. For children with incomplete immunization according to the province of Alberta schedule, the reasons for such were clarified. Demographic data and age at diagnosis were also collected. Immunization records were obtained from 145 (79%) children with IBD. Fifteen children had incomplete routine childhood immunizations, including two with no previous immunizations. The most common incomplete immunizations included hepatitis B (n=9), diphtheria, tetanus, acellular pertussis at 14 to 16 years of age (n=7), and diphtheria, tetanus, acellular pertussis, inactivated polio at four to six years of age (n=6). The reasons for incomplete immunization included use of immunosuppressive therapy at time of scheduled immunization; IBD-related symptoms at time of scheduled immunization; parental refusal; recent move from elsewhere with different immunization schedule; unawareness of routine immunization; and needle phobia. Although the majority of children with IBD had complete childhood immunizations, suboptimal immunizations were present in 10%. With increasing use of immunosuppressive therapy in IBD, physicians caring for children with IBD must periodically evaluate immunization status and ensure the completeness of childhood immunizations.

  15. Tricking the guard: exploiting plant defense for disease susceptibility.

    Science.gov (United States)

    Lorang, J; Kidarsa, T; Bradford, C S; Gilbert, B; Curtis, M; Tzeng, S-C; Maier, C S; Wolpert, T J

    2012-11-02

    Typically, pathogens deploy virulence effectors to disable defense. Plants defeat effectors with resistance proteins that guard effector targets. We found that a pathogen exploits a resistance protein by activating it to confer susceptibility in Arabidopsis. The guard mechanism of plant defense is recapitulated by interactions among victorin (an effector produced by the necrotrophic fungus Cochliobolus victoriae), TRX-h5 (a defense-associated thioredoxin), and LOV1 (an Arabidopsis susceptibility protein). In LOV1's absence, victorin inhibits TRX-h5, resulting in compromised defense but not disease by C. victoriae. In LOV1's presence, victorin binding to TRX-h5 activates LOV1 and elicits a resistance-like response that confers disease susceptibility. We propose that victorin is, or mimics, a conventional pathogen virulence effector that was defeated by LOV1 and confers virulence to C. victoriae solely because it incites defense.

  16. Modeling elm growth and Dutch elm disease susceptibility

    Science.gov (United States)

    Alberto Santini; Luisa Ghelardini

    2012-01-01

    Elm susceptibility to Dutch elm disease (DED) displays strong seasonal variation. The period during which elms can become infected and express DED symptoms is generally restricted to several weeks after growth resumption in spring, although it can vary among species, provenances, and environmental conditions. The reason for this phenomenon is not understood, but the...

  17. Exploration of genetic susceptibility factors for Parkinson's disease

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 89; Issue 2. Exploration of genetic susceptibility factors for Parkinson's disease in a South American sample. Bruno A. Benitez Diego A. Forero Gonzalo H. Arboleda Luis A. Granados Juan J. Yunis William Fernandez Humberto Arboleda. Research Note Volume 89 Issue 2 ...

  18. Barley disease susceptibility factor RACB acts in epidermal cell polarity and positioning of the nucleus.

    Science.gov (United States)

    Scheler, Björn; Schnepf, Vera; Galgenmüller, Carolina; Ranf, Stefanie; Hückelhoven, Ralph

    2016-05-01

    RHO GTPases are regulators of cell polarity and immunity in eukaryotes. In plants, RHO-like RAC/ROP GTPases are regulators of cell shaping, hormone responses, and responses to microbial pathogens. The barley (Hordeum vulgare L.) RAC/ROP protein RACB is required for full susceptibility to penetration by Blumeria graminis f.sp. hordei (Bgh), the barley powdery mildew fungus. Disease susceptibility factors often control host immune responses. Here we show that RACB does not interfere with early microbe-associated molecular pattern-triggered immune responses such as the oxidative burst or activation of mitogen-activated protein kinases. RACB also supports rather than restricts expression of defence-related genes in barley. Instead, silencing of RACB expression by RNAi leads to defects in cell polarity. In particular, initiation and maintenance of root hair growth and development of stomatal subsidiary cells by asymmetric cell division is affected by silencing expression of RACB. Nucleus migration is a common factor of developmental cell polarity and cell-autonomous interaction with Bgh RACB is required for positioning of the nucleus near the site of attack from Bgh We therefore suggest that Bgh profits from RACB's function in cell polarity rather than from immunity-regulating functions of RACB. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  19. Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation.

    Science.gov (United States)

    Straubinger, Kathrin; Paul, Sabine; Prazeres da Costa, Olivia; Ritter, Manuel; Buch, Thorsten; Busch, Dirk H; Layland, Laura E; Prazeres da Costa, Clarissa U

    2014-12-01

    Schistosomiasis, a chronic helminth infection, elicits distinct immune responses within the host, ranging from an initial TH1 and subsequent TH2 phase to a regulatory state, and is associated with dampened allergic reactions within the host. We sought to evaluate whether non-transplacental helminth infection during pregnancy alters the offspring's susceptibility to allergy. Ovalbumin-induced allergic airway inflammation was analyzed in offspring from Schistosoma mansoni-infected mothers mated during the TH1, TH2, or regulatory phase of infection. Embryos derived from in vitro fertilized oocytes of acutely infected females were transferred into uninfected foster mice to determine the role of placental environment. The fetomaternal unit was further characterized by helminth-specific immune responses and microarray analyses. Eventually, IFN-γ-deficient mice were infected to evaluate the role of this predominant cytokine on the offspring's allergy phenotype. We demonstrate that offspring from schistosome-infected mothers that were mated in the TH1 and regulatory phases, but not the TH2 immune phase, are protected against the onset of allergic airway inflammation. Interestingly, these effects were associated with distinctly altered schistosome-specific cytokine and gene expression profiles within the fetomaternal interface. Furthermore, we identified that it is not the transfer of helminth antigens but rather maternally derived IFN-γ during the acute phase of infection that is essential for the progeny's protective immune phenotype. Overall, we present a novel immune phase-dependent coherency between the maternal immune responses during schistosomiasis and the progeny's predisposition to allergy. Therefore, we propose to include helminth-mediated transmaternal immune modulation into the expanded hygiene hypothesis. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Are happy chickens safer chickens? Poultry welfare and disease susceptibility.

    Science.gov (United States)

    Humphrey, Tom

    2006-08-01

    1. Contaminated chicken meat remains an internationally important vehicle for human infection with Salmonella and Campylobacter spp. In addition, the last 20 years has seen an international pandemic of human salmonellosis caused by the contamination of eggs with Salmonella Enteritidis. 2. It has been a long held scientific view that Campylobacter spp. and most, if not all of the common zoonotic salmonella, are essentially commensal in chickens. They usually form part of the gut flora and contaminate chicken carcases, for example, by faecal spillage at slaughter. Even when certain salmonella serovars like S. Enteritidis are invasive in laying hens overt evidence of clinical disease is rare and the birds appear to behave normally. 3. Are these bacteria just 'passing through' the avian host and only transient members of the bacterial flora or is there a more dynamic perspective to this infection/colonisation process? Chickens mount antibody responses to both pathogens, which indicate something other than commensalism. Such immune responses, however, do not always result in the clearance of the pathogen. 4. Not all animals in a group will carry salmonella or campylobacter, even under experimental conditions, and will vary, especially those that are outbred, in their responses to pathogen challenge. Identifying the reasons behind this could have important implications for disease control. 5. Both salmonella and campylobacter are more likely to be found in animals, which are compromised and this may explain at least part of the variations seen. Animals are more susceptible to infection when they are in a poor environment, fed a poor diet and/or under physical or psychological stress. 6. Work in this area has naturally focused on pathogens of medical significance and has shown that neurotransmitters such as noradrenaline can markedly alter pathogen behaviour. Other host responses like Interferon gamma can also affect host tissues in a way, which facilitates invasion by

  1. The Role of CD39 in Modulating Effector Immune Responses in Inflammatory Bowel Disease

    OpenAIRE

    Huang, Huang

    2015-01-01

    Inflammatory bowel disease is associated with excessive inflammation of the bowel and intestinal tissues in genetically susceptible individuals. IBD can manifest in two major forms, ulcerative colitis and Crohn’s disease. T helper type 17 cells (Th17) are effector lymphocytes that have been linked to intestinal inflammation in both mice and humans. Effector Th17 cells and regulatory T cells (Treg) – a subset pivotal to immune-tolerance maintenance – derive from the same CD4 progenitors. Our i...

  2. Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility.

    Science.gov (United States)

    Noreen, Mamoona; Arshad, Muhammad

    2015-06-01

    Toll like receptors (TLRs) play a crucial role in regulation of innate as well as adaptive immunity. TLRs recognize a distinct but limited repertoire of conserved microbial products. Ligand binding to TLRs activates the signaling cascade and results in activation of multiple inflammatory genes. Variation in this immune response is under genetic control. Polymorphisms in genes associated with inflammatory pathway especially influence the outcome of diseases. TLR2 makes heterodimer with TLR1 or TLR6 and recognizes a wide variety of microbial ligands. In this review, we summarize studies of polymorphisms in genes encoding TLR1, TLR2, TLR4, TLR6, and most polymorphic adaptor protein, Mal/TIRAP, revealing their effect on susceptibility to diseases.

  3. Characteristics of Japanese inflammatory bowel disease susceptibility loci.

    Science.gov (United States)

    Arimura, Yoshiaki; Isshiki, Hiroyuki; Onodera, Kei; Nagaishi, Kanna; Yamashita, Kentaro; Sonoda, Tomoko; Matsumoto, Takayuki; Takahashi, Atsushi; Takazoe, Masakazu; Yamazaki, Keiko; Kubo, Michiaki; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

    2014-08-01

    There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD. For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn's disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls. We confirmed that the NKX2-3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24). Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

  4. Review: Potential biotechnological assets related to plant immunity modulation applicable in engineering disease-resistant crops.

    Science.gov (United States)

    Silva, Marilia Santos; Arraes, Fabrício Barbosa Monteiro; Campos, Magnólia de Araújo; Grossi-de-Sa, Maira; Fernandez, Diana; Cândido, Elizabete de Souza; Cardoso, Marlon Henrique; Franco, Octávio Luiz; Grossi-de-Sa, Maria Fátima

    2018-05-01

    This review emphasizes the biotechnological potential of molecules implicated in the different layers of plant immunity, including, pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), effector-triggered susceptibility (ETS), and effector-triggered immunity (ETI) that can be applied in the development of disease-resistant genetically modified (GM) plants. These biomolecules are produced by pathogens (viruses, bacteria, fungi, oomycetes) or plants during their mutual interactions. Biomolecules involved in the first layers of plant immunity, PTI and ETS, include inhibitors of pathogen cell-wall-degrading enzymes (CWDEs), plant pattern recognition receptors (PRRs) and susceptibility (S) proteins, while the ETI-related biomolecules include plant resistance (R) proteins. The biomolecules involved in plant defense PTI/ETI responses described herein also include antimicrobial peptides (AMPs), pathogenesis-related (PR) proteins and ribosome-inhibiting proteins (RIPs), as well as enzymes involved in plant defensive secondary metabolite biosynthesis (phytoanticipins and phytoalexins). Moreover, the regulation of immunity by RNA interference (RNAi) in GM disease-resistant plants is also considered. Therefore, the present review does not cover all the classes of biomolecules involved in plant innate immunity that may be applied in the development of disease-resistant GM crops but instead highlights the most common strategies in the literature, as well as their advantages and disadvantages. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

    Science.gov (United States)

    Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

    2014-11-11

    Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

  6. Immune Development and Intestinal Microbiota in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Tamara Pozo-Rubio

    2012-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding, infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.

  7. In immune defense: redefining the role of the immune system in chronic disease.

    Science.gov (United States)

    Rubinow, Katya B; Rubinow, David R

    2017-03-01

    The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

  8. Helminthic therapy: using worms to treat immune-mediated disease.

    Science.gov (United States)

    Elliott, David E; Weinstock, Joel V

    2009-01-01

    There is an epidemic of immune-mediated disease in highly-developed industrialized countries. Such diseases, like inflammatory bowel disease, multiple sclerosis and asthma increase in prevalence as populations adopt modern hygienic practices. These practices prevent exposure to parasitic worms (helminths). Epidemiologic studies suggest that people who carry helminths have less immune-mediated disease. Mice colonized with helminths are protected from disease in models of colitis, encephalitis, Type 1 diabetes and asthma. Clinical trials show that exposure to helminths reduce disease activity in patients with ulcerative colitis or Crohn's disease. This chapter reviews some of the work showing that colonization with helminths alters immune responses, against dysregulated inflammation. These helminth-host immune interactions have potentially important implications for the treatment of immune-mediated diseases.

  9. Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

    Science.gov (United States)

    Kirchner, Elizabeth; Ruffing, Victoria

    2017-02-01

    For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Infection's Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility.

    Science.gov (United States)

    Taylor, Steven L; McGuckin, Michael A; Wesselingh, Steve; Rogers, Geraint B

    2018-02-01

    Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host-pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  12. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

    Science.gov (United States)

    Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Jun, Gyungah; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Denning, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Vronskaya, Maria; Johnson, Andrew D; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Hernández, Isabel; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick C; Hardy, John; Naranjo, Maria Candida Deniz; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Scarpini, Elio; Bonuccelli, Ubaldo; Mancuso, Michelangelo; Siciliano, Gabriele; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Frank-García, Ana; Panza, Francesco; Solfrizzi, Vincenzo; Caffarra, Paolo; Nacmias, Benedetta; Perry, William; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Van Broeckhoven, Christine; Farrer, Lindsay A; van Duijn, Cornelia M; Ramirez, Alfredo; Seshadri, Sudha; Schellenberg, Gerard D; Amouyel, Philippe; Williams, Julie

    2014-01-01

    Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

  13. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Valentina Escott-Price

    Full Text Available Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6 and 14 (IGHV1-67 p = 7.9×10-8 which indexed novel susceptibility loci.The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

  14. Association between rs6812193 polymorphism and sporadic Parkinson's disease susceptibility.

    Science.gov (United States)

    Huo, Qiang; Li, Tao; Zhao, Peiqing; Wang, Lianqing

    2015-08-01

    Recently, the association of a single nucleotide polymorphism rs6812193 C/T with sporadic Parkinson's disease (PD) susceptibility has been widely evaluated, but the results remained inconsistent. This association should be clarified because of the importance of it on human health and quality of life. We performed a comprehensive meta-analysis to evaluate the association between the rs6812193 polymorphism and sporadic PD. PubMed was used to retrieve articles published up to June 2014 for all studies evaluating the rs6812193 polymorphism and PD in humans. Ethnicity-specific subgroup analysis was also performed based on ethnicity susceptibility. A total of 17 independent study samples (15 Caucasians and 2 Asians) including 17,956 cases and 52,751 controls were used in the presented study. The MAFT (minor allele T frequency) in PD patients of European descent is obviously higher than Asian cases (p susceptibility among overall samples (OR 0.882, 95 % CI 0.856-0.908) and Caucasian population (OR 0.881, 95 % CI 0.856-0.907), but not in Asian samples (OR 0.918, 95 % CI 0.721-1.168). No evidence of publication bias was observed. Throughout our analysis, the rs6812193 polymorphism is significantly associated with sporadic PD susceptibility in Caucasian samples, and ethnicity might be the key point of inconsistency in rs6812193 studies. Further studies are warranted to re-examine the observed associations, especially in different ethnicities.

  15. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  16. Microparticles as immune regulators in infectious disease

    Directory of Open Access Journals (Sweden)

    Zheng Lung Ling

    2011-11-01

    Full Text Available Despite their clear relationship to immunology, few existing studies have examined potential role of microparticles (MP in infectious disease. Infection with pathogens usually leads to the expression of a range of inflammatory cytokines and chemokines, as well as significant stress in both infected and uninfected cells. It is thus reasonable to infer from studies to date that infection-associated inflammation also leads to MP production. MP are produced by most of the major cell types in the immune system, and appear to be involved at both the innate and adaptive levels, potentially serving different functions at each level. Thus, MP do not appear to have a universal function; instead their functions are source- or stimulus-dependent, although likely to be primarily either pro- or anti-inflammatory. Importantly, in infectious diseases MP may have the ability to deliver antigen to APC via the biological cargo acquired from their cells of origin. Another potential benefit of MP would be to transfer and/or disseminate phenotype and function to target cells. However, MP may also potentially be manipulated, particularly by intracellular pathogens for survival advantage.

  17. Influence of the factor V Leiden mutation on infectious disease susceptibility and outcome

    DEFF Research Database (Denmark)

    Benfield, Thomas L; Dahl, Mortens; Nordestgaard, Borge G

    2005-01-01

    The effect of the coagulation factor V Leiden mutation on infectious disease susceptibility and outcome is controversial.......The effect of the coagulation factor V Leiden mutation on infectious disease susceptibility and outcome is controversial....

  18. Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

    Science.gov (United States)

    Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

    2018-01-01

    Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions

  19. Global Immunizations: Health Promotion and Disease Prevention Worldwide.

    Science.gov (United States)

    Macintosh, Janelle L B; Eden, Lacey M; Luthy, Karlen E; Schouten, Aimee E

    Immunizations are one of the most important health interventions of the 20th century, yet people in many areas of the world do not receive adequate immunizations. Approximately 3 million people worldwide die every year from vaccine-preventable diseases; about half of these deaths are young children and infants. Global travel is more common; diseases that were once localized now can be found in communities around the world. Multiple barriers to immunizations have been identified. Healthcare access, cost, and perceptions of safety and trust in healthcare are factors that have depressed global immunization rates. Several global organizations have focused on addressing these barriers as part of their efforts to increase immunization rates. The Bill and Melinda Gates Foundation, The World Health Organization, and the United Nations Children's Emergency Fund each have a part of their organization that is concentrated on immunizations. Maternal child nurses worldwide can assist in increasing immunization rates. Nurses can participate in outreach programs to ease the burden of patients and families in accessing immunizations. Nurses can work with local and global organizations to make immunizations more affordable. Nurses can improve trust and knowledge about immunizations in their local communities. Nurses are a powerful influence in the struggle to increase immunization rates, which is a vital aspect of global health promotion and disease prevention.

  20. The peritoneum: healing, immunity, and diseases.

    Science.gov (United States)

    Capobianco, Annalisa; Cottone, Lucia; Monno, Antonella; Manfredi, Angelo A; Rovere-Querini, Patrizia

    2017-10-01

    The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Innate and Adaptive Immune Response to Pneumonia Virus of Mice in a Resistant and a Susceptible Mouse Strain

    Directory of Open Access Journals (Sweden)

    Ellen R. T. Watkiss

    2013-01-01

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM.

  2. CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood

    Science.gov (United States)

    Alves, Lívia A.; Nomura, Ryota; Mariano, Flávia S.; Harth-Chu, Erika N.; Stipp, Rafael N.; Nakano, Kazuhiko

    2016-01-01

    Streptococcus mutans, a major pathogen of dental caries, may promote systemic infections after accessing the bloodstream from oral niches. In this study, we investigate pathways of complement immunity against S. mutans and show that the orphan regulator CovR (CovRSm) modulates susceptibility to complement opsonization and survival in blood. S. mutans blood isolates showed reduced susceptibility to C3b deposition compared to oral isolates. Reduced expression of covRSm in blood strains was associated with increased transcription of CovRSm-repressed genes required for S. mutans interactions with glucans (gbpC, gbpB, and epsC), sucrose-derived exopolysaccharides (EPS). Consistently, blood strains showed an increased capacity to bind glucan in vitro. Deletion of covRSm in strain UA159 (UAcov) impaired C3b deposition and binding to serum IgG and C-reactive protein (CRP) as well as phagocytosis through C3b/iC3b receptors and killing by neutrophils. Opposite effects were observed in mutants of gbpC, epsC, or gtfBCD (required for glucan synthesis). C3b deposition on UA159 was abolished in C1q-depleted serum, implying that the classical pathway is essential for complement activation on S. mutans. Growth in sucrose-containing medium impaired the binding of C3b and IgG to UA159, UAcov, and blood isolates but had absent or reduced effects on C3b deposition in gtfBCD, gbpC, and epsC mutants. UAcov further showed increased ex vivo survival in human blood in an EPS-dependent way. Consistently, reduced survival was observed for the gbpC and epsC mutants. Finally, UAcov showed an increased ability to cause bacteremia in a rat model. These results reveal that CovRSm modulates systemic virulence by regulating functions affecting S. mutans susceptibility to complement opsonization. PMID:27572331

  3. Myocarditis in auto-immune or auto-inflammatory diseases.

    Science.gov (United States)

    Comarmond, Cloé; Cacoub, Patrice

    2017-08-01

    Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis.

    Science.gov (United States)

    Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT". © Society for Leukocyte Biology.

  5. Diversity of aging of the immune system classified in the cotton rat (Sigmodon hispidus) model of human infectious diseases.

    NARCIS (Netherlands)

    Guichelaar, Teun; van Erp, Elisabeth A; Hoeboer, Jeroen; Smits, Noortje A M; van Els, Cécile A C M; Pieren, Daan K J; Luytjes, Willem

    2018-01-01

    Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed

  6. Role of the Immune System in Diabetic Kidney Disease.

    Science.gov (United States)

    Hickey, Fionnuala B; Martin, Finian

    2018-03-12

    The purpose of this review is to examine the proposed role of immune modulation in the development and progression of diabetic kidney disease (DKD). Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies. In addition, increased levels of circulating pro-inflammatory cytokines have been linked to disease progression. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease. Although no current therapies for DKD are directly based on immune modulation many of the therapies in clinical use have anti-inflammatory effects along with their primary actions. Macrophages emerge as the most likely beneficial immune cell target and compounds which reduce macrophage infiltration to the kidney have shown potential in both animal models and clinical trials.

  7. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs

    Directory of Open Access Journals (Sweden)

    Wen-I Lee

    2011-12-01

    Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively

  8. [Genetics and susceptibility to human papillomaviruses: epidermodysplasia verruciformis, a disease model].

    Science.gov (United States)

    Orth, Gérard

    2010-06-01

    The outcomes of infection by human papillomaviruses (HPV), both oncogenic and non oncogenic, show major interindividual variability The underlying genetic factors and mechanisms are poorly known, but their complexity is illustrated by epidermodysplasia verruciformis (EV), a rare autosomal recessive genodermatosis associated with a high risk of non melanoma skin cancer. This model disease is characterized by abnormal susceptibility to widespread betapapillomaviruses, including HPV-5, a virus associated with EV cancers. Most cases of EV are caused by a mutation that inactivates either of two related genes, EVER1 and EVER2. This inactivation likely compensates for the absence of a viral gene (E5 or E8) essential for HPV pathogenicity. Proteins E5 and E8 interfere with the interaction between EVER proteins and ZnT1, a zinc transporter EV is thus likely to represent a primary defect of intrinsic (constitutive) immunity or innate immunity to betapapillomaviruses, involving modulation of zinc homeostasis upon keratinocyte infection. It remains to be established which cellular genes are involved in intrinsic, innate or acquired immune responses to other human papillomaviruses, including oncogenic genital types.

  9. Comprehensive analysis of three TYK2 gene variants in the susceptibility to Chagas disease infection and cardiomyopathy

    Science.gov (United States)

    Carmona, F. David; Dolade, Nuria; Vargas, Sofia; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2018-01-01

    Tyrosine kinase 2 (TYK2) is a member of the Janus kinases family implicated in the signal transduction of type I interferons and several interleukins. It has been described that genetic mutations within TYK2 lead to multiple deleterious effects in the immune response. In this work, we have analyzed three functional independent variants from the frequency spectrum on the TYK2 gene (common and low-frequency variants) suggested to reduce the function of the gene in mediating cytokine signaling and the susceptibility to infections by Trypanosoma cruzi and/or the development of Chagas cardiomyopathy in the Colombian population. A total of 1,323 individuals from a Colombian endemic region for Chagas disease were enrolled in the study. They were classified as seronegative (n = 445), seropositive asymptomatic (n = 336), and chronic Chagas Cardiomyopathy subjects (n = 542). DNA samples were genotyped using TaqMan probes. Our results showed no statistically significant differences between the allelic frequencies of the three analyzed variants when seropositive and seronegative individuals were compared, therefore these variants were not associated with susceptibility to Chagas disease. Moreover, when Chagas cardiomyopathy patients were compared to asymptomatic patients, no significant associations were found. Previous reports highlighted the association of this gene in immune-related disorders under an autoimmunity context, but not predisposing patients to infectious diseases, which is consistent with our findings. Therefore, according to our results, TYK2 gene variants do not seem to play an important role in Chagas disease susceptibility and/or chronic Chagas cardiomyopathy. PMID:29304122

  10. Genetic variants of CD209 associated with Kawasaki disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Ho-Chang Kuo

    Full Text Available BACKGROUND: Kawasaki disease (KD is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209 in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. METHODS: A total of 948 subjects (381 KD and 567 controls were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804 were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL and intravenous immunoglobulin (IVIG treatment outcomes were collected for analysis. RESULTS: Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240 and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61 and G/A/G haplotype (P = 0.0365, OR = 1.52 had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. CONCLUSION: CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.

  11. Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility

    Science.gov (United States)

    Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

    2014-01-01

    Background Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. Methods A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Results Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. Conclusion CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness. PMID:25148534

  12. Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

    Science.gov (United States)

    Xu, Joella; Huang, Guannan; Guo, Tai L.

    2016-01-01

    Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg) cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS), have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases. PMID:29051427

  13. Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

    Directory of Open Access Journals (Sweden)

    Joella Xu

    2016-09-01

    Full Text Available Bisphenol A (BPA, used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors, epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS, have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases.

  14. Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

    Science.gov (United States)

    Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

    2018-01-01

    Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around

  15. Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

    Science.gov (United States)

    Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

    2018-01-01

    Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD

  16. Linking the microbiota, chronic disease and the immune system

    Science.gov (United States)

    Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

    2016-01-01

    Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

  17. PPARgamma in immunity and inflammation: cell types and diseases.

    Science.gov (United States)

    Széles, Lajos; Töröcsik, Dániel; Nagy, László

    2007-08-01

    The lipid activated transcription factor, PPARgamma appears to have multiple functions in the immune system. There are several cell types expressing the receptor, most prominently antigen presenting cells, such as macrophages and dendritic cells. The receptor's activation leads to primary transcriptional activation of many, mostly lipid metabolism-related genes. However, gene regulation also occurs on immunity and inflammation-related genes. Key questions are: in what way lipid metabolism and immune regulation are connected and how activation and/or repression of gene expression may modulate inflammatory and anti-inflammatory responses and in what way can these be utilized in therapy. Here we provide a cell type and disease centric review on the role of this lipid activated transcription factor in the various cells of the immune system it is expressed in, and in some major inflammatory diseases such as atherosclerosis, inflammatory bowel disease and rheumatoid arthritis.

  18. KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility

    Science.gov (United States)

    Ragazzo, Michele; Manzo, Laura; Costanza, Gaetana; Bowes, John; Hüffmeier, Ulrike; Potenza, Saverio; Sangiuolo, Federica; Reis, André; Barton, Anne; Novelli, Giuseppe; Orlandi, Augusto; Giardina, Emiliano

    2017-01-01

    To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis. PMID:29221136

  19. Additional mechanisms conferring genetic susceptibility to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Miguel eCalero

    2015-04-01

    Full Text Available Familial Alzheimer's disease (AD, mostly associated with early onset, is caused by mutations in three genes (APP, PSEN1 and PSEN2 involved in the production of the amyloid  peptide. In contrast, the molecular mechanisms that trigger the most common late onset sporadic AD remain largely unknown. With the implementation of an increasing number of case-control studies and the upcoming of large-scale genome-wide association studies (GWAS there is a mounting list of genetic risk factors associated to common genetic variants that have been associated to sporadic AD. Besides APOE, that presents a strong association with the disease (OR~4, the rest of these genes have moderate or low degrees of association, with OR ranging from 0.88 to 1.23. Taking together, these genes may account only for a fraction of the attributable AD risk and therefore, rare variants and epistastic gene interactions should be taken into account in order to get the full picture of the genetic risks associated to AD. Here, we review recent whole-exome studies looking for rare variants, somatic brain mutations with a strong association to the disease, and several studies dealing with epistasis as additional mechanisms conferring genetic susceptibility to AD. Altogether, recent evidence underlines the importance of defining molecular and genetic pathways and networks rather than the contribution of specific genes.

  20. Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

    Science.gov (United States)

    Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

    2000-01-01

    Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

  1. Cardiovascular Disease Susceptibility and Resistance in Circumpolar Inuit Populations.

    Science.gov (United States)

    Tvermosegaard, Maria; Dahl-Petersen, Inger K; Nielsen, Nina Odgaard; Bjerregaard, Peter; Jørgensen, Marit Eika

    2015-09-01

    Cardiovascular disease (CVD) is a major public health issue in indigenous populations in the Arctic. These diseases have emerged concomitantly with profound social changes over the past 60 years. The aim of this study was to summarize the literature on CVD risk among Arctic Inuit. Literature on prevalence, incidence, and time trends for CVD and its risk factors in Arctic Inuit populations was reviewed. Most evidence supports a similar incidence of coronary heart disease and a higher incidence of cerebrovascular disease among Arctic Inuit than seen in western populations. Factors that may increase CVD risk include aging of the population, genetic susceptibility, and a rapid increase in obesity, diabetes, and hypertension in parallel with decreasing physical activity and deterioration of the lipid profile. In contrast, and of great importance, there has been a decrease in smoking and alcohol intake (at least documented in Greenland), and contaminant levels are declining. Although there have been marked socioeconomic and dietary changes, it remains unsolved and to some extent controversial how this may have influenced cardiovascular risk among Arctic Inuit. The increase in life expectancy, in combination with improved prognosis for patients with manifest CVD, will inevitably lead to a large increase in absolute numbers of individuals affected by CVD in Arctic Inuit populations, exacerbated by the rise in most CVD risk factors over the past decades. For preventive purposes and for health care planning, it is crucial to carefully monitor disease incidence and trends in risk factors in these vulnerable Arctic populations. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  2. GENETIC SUSCEPTIBILITY TO RESPIRATORY SYNCYTIAL VIRUS BRONCHIOLITIS IN PRETERM CHILDREN IS ASSOCIATED WITH AIRWAY REMODELING GENES AND INNATE IMMUNE GENES

    NARCIS (Netherlands)

    Siezen, Christine L. E.; Bont, Louis; Hodemaekers, Hennie M.; Ermers, Marieke J.; Doornbos, Gerda; van't Slot, Ruben; Wijmenga, Ciska; van Hottwelingen, Hans C.; Kimpen, Jan L. L.; Kimman, Tjeerd G.; Hoebee, Barbara; Janssen, Riny

    Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2. IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease

  3. Wild rodents as a model to discover genes and pathways underlying natural variation in infectious disease susceptibility.

    Science.gov (United States)

    Turner, A K; Paterson, S

    2013-11-01

    Individuals vary in their susceptibility to infectious disease, and it is now well established that host genetic factors form a major component of this variation. The discovery of genes underlying susceptibility has the potential to lead to improved disease control, through the identification and management of vulnerable individuals and the discovery of novel therapeutic targets. Laboratory rodents have proved invaluable for ascertaining the function of genes involved in immunity to infection. However, these captive animals experience conditions very different to the natural environment, lacking the genetic diversity and environmental pressures characteristic of natural populations, including those of humans. It has therefore often proved difficult to translate basic laboratory research to the real world. In order to further our understanding of the genetic basis of infectious disease resistance, and the evolutionary forces that drive variation in susceptibility, we propose that genetic research traditionally conducted on laboratory animals is expanded to the more ecologically valid arena of natural populations. In this article, we highlight the potential of using wild rodents as a new resource for biomedical research, to link the functional genetic knowledge gained from laboratory rodents with the variation in infectious disease susceptibility observed in humans and other natural populations. © 2013 John Wiley & Sons Ltd.

  4. For better or worse: Immune system involvement in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Emma L. Walton

    2018-02-01

    Full Text Available In this issue of the Biomedical Journal, we explore the key role of the immune system in the development of Alzheimer's disease. We also learn more about the link between two disorders related to metabolic imbalances, with findings that could help to inform future screening programs. Finally, we would like to highlight some big news for our journal: the Biomedical Journal will be indexed in the Science Citation Index and receive its first official impact factor from this year. Keywords: Alzheimer's disease, Tau, Immune responses, Subclinical hypothyroidism, Metabolic disease

  5. Immune Deficiency Disease' of Undetermined Aetiology in Infancy

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... J., 48, 687 (1974). Immune deficiency diseases in infancy are best known as ... tion at the age of 10 months confirmed the mental retarda- tion, and on further ... Examination of other organ systems was non-contributory. Triple .... linked recessive transmitted disease, and has not been re- ported in females.

  6. Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population.

    Science.gov (United States)

    Aiba, Yoshihiro; Yamazaki, Keiko; Nishida, Nao; Kawashima, Minae; Hitomi, Yuki; Nakamura, Hitomi; Komori, Atsumasa; Fuyuno, Yuta; Takahashi, Atsushi; Kawaguchi, Takaaki; Takazoe, Masakazu; Suzuki, Yasuo; Motoya, Satoshi; Matsui, Toshiyuki; Esaki, Motohiro; Matsumoto, Takayuki; Kubo, Michiaki; Tokunaga, Katsushi; Nakamura, Minoru

    2015-09-01

    We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn's diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10(-2) and P=8.40 × 10(-3), respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10(-2), P=3.88 × 10(-2) and P=2.04 × 10(-2), respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases.

  7. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Celiac Disease Presenting with Immune Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Hakan Sarbay

    2017-01-01

    Full Text Available Celiac disease (CD is an immunological disorder. Clinical manifestations occur as a result of intestinal mucosa damage and malabsorption. CD is also associated with extraintestinal manifestations and autoimmune disorders. The coexistence of CD and autoimmune diseases has been described before. In this article, a patient with CD presenting with thrombocytopenia is discussed.

  9. Innate immune responses against foot-and-mouth disease virus: current understanding and future directions.

    Science.gov (United States)

    Summerfield, Artur; Guzylack-Piriou, Laurence; Harwood, Lisa; McCullough, Kenneth C

    2009-03-15

    Foot-and-mouth disease (FMD) represents one of the most economically important diseases of farm animals. The basis for the threat caused by this virus is the high speed of replication, short incubation time, high contagiousness, and high mutation rate resulting in constant antigenic changes. Thus, although protective immune responses against FMD virus (FMDV) can be efficacious, the rapidity of virus replication and spread can outpace immune defence development and overrun the immune system. FMDV can also evade innate immune responses through its ability to shut down cellular protein synthesis, including IFN type I, in susceptible epithelial cells. This is important for virus evolution, as FMDV is quite sensitive to the action of IFN. Despite this, innate immune responses are probably induced in vivo, although detailed studies on this subject are lacking. Accordingly, this interaction of FMDV with cells of the innate immune system is of particular interest. Dendritic cells (DC) can be infected by FMDV and support viral RNA replication, and viral protein synthesis but the latter is inefficient or abortive, leading most often to incomplete replication and progeny virus release. As a result DC can be activated, and particularly in the case of plasmacytoid DC (pDC), this is manifest in terms of IFN-alpha release. Our current state of knowledge on innate immune responses induced by FMDV is still only at a relatively early stage of understanding. As we progress, the investigations in this area will help to improve the design of current vaccines and the development of novel control strategies against FMD.

  10. Natural immunity and HIV disease progression

    DEFF Research Database (Denmark)

    Ullum, H; Cozzi-Lepri, A; Aladdin, H

    1999-01-01

    OBJECTIVE: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1. DESIGN: Data used were from 172 individuals with an estimated measure of NK cell activity...... and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.0 years. METHODS: The lytic activity of NK cells and LAK cells, the CD4 T lymphocyte count, and the concentration of CD......16/CD56 NK cells were measured at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis was performed considering three main endpoints: CD4 cell counts below 100 x 10(6) cells/l, clinical AIDS, and death. RESULTS: In unadjusted analysis and after adjustment for age, CD4 T...

  11. GAB2 as an Alzheimer Disease Susceptibility Gene

    Science.gov (United States)

    Schjeide, Brit-Maren M.; Hooli, Basavaraj; Parkinson, Michele; Hogan, Meghan F.; DiVito, Jason; Mullin, Kristina; Blacker, Deborah; Tanzi, Rudolph E.; Bertram, Lars

    2009-01-01

    Background Genomewide association (GWA) studies have recently implicated 4 novel Alzheimer disease (AD) susceptibility loci (GAB2, GOLM1, and 2 uncharacterized loci to date on chromosomes 9p and 15q). To our knowledge, these findings have not been independently replicated. Objective To assess these GWA findings in 4 large data sets of families affected by AD. Design Follow-up of genetic association findings in previous studies. Setting Academic research. Participants More than 4000 DNA samples from almost 1300 families affected with AD. Main Outcome Measures Genetic association analysis testing of 4 GWA signals (rs7101429 [GAB2], rs7019241 [GOLM1], rs10519262 [chromosome 15q], and rs9886784 [chromosome 9p]) using family-based methods. Results In the combined analyses, only rs7101429 in GAB2 yielded significant evidence of association with the same allele as in the original GWA study (P = .002). The results are in agreement with recent meta-analyses of this and other GAB2 polymorphisms suggesting approximately a 30% decrease in risk for AD among carriers of the minor alleles. None of the other 3 tested loci showed consistent evidence for association with AD across the investigated data sets. Conclusions GAB2 contains genetic variants that may lead to a modest change in the risk for AD. Despite these promising results, more data from independent samples are needed to better evaluate the potential contribution of GAB2 to AD risk in the general population. PMID:19204163

  12. The role of acquired immunity and periodontal disease progression.

    Science.gov (United States)

    Teng, Yen-Tung A

    2003-01-01

    Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response-in particular, CD4+ T-cells-plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction. In particular, studies of the pathogen-specific CD4+ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4+ T-cell-mediated osteoclastogenic factor, 'RANK-L', which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8+ T-cells, and CD4+ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

  13. Clinical application of MR susceptibility weighted imaging in cerebrovascular diseases

    International Nuclear Information System (INIS)

    Zhu Wenzhen; Qi Jianpin; Shen Hao; Wang Chengyuan; Xia Liming; Hu Junwu; Feng Dingyi

    2007-01-01

    Objective: To assess clinical application value of susceptibility weighted imaging (SWI) in cerebrovascular diseases. Method: Twenty-three patients with cerebrovascular disease were investigated, including 7 cases of cavernoma, 4 of venous hemangioma, 3 of small AVM, 1 of Sturge-Weber Syndrome, 2 of cerebral venous sinus thrombosis and 6 of chronic cerebral infarction. All patients underwent standard Mill and SWI, and most of them also underwent enhanced T 1 WI and MRA. The corrected phase (CP) values were obtained at the lesions and control areas. Results: The average CP values of the lesions and the control areas were -0.112±0.032 and -0.013±0.004, respectively (t=2.167, P 2 WI. The cavemoma could be differentiated from the hemorrhage within lesions. Moreover, multiple microcavernomas were detected on SWI. In 4 cases of venous hemangioma, SWI detected spider-like lesions with more hair-thin pulp veins adjacent to the dilated draining vein than contrast MRI. In 3 cases of small AVM, SWI was more advantageous than MRA in clearly detecting the small feeding artery. In 1 case of Sturge-Weber Syndrome, SWI demonstrated large areas of calcification and the abnormal vessels on the cerebral surface and the deep part of the cerebrum at the same time. In 2 cases of cerebral venous sinus thrombosis, the deep draining veins and superficial venous rete were generally dilated and winding, and the hemorrhagic lesions could be detected earlier than conventional MR images in one case. In 6 eases of cerebral infarction, old hemorrhage was clearly displayed within the lesions. Conclusion: SWI has more predominant advantages than conventional MRI and MRA in detecting the low-flow cerebral vascular malformations, identifying microbleeds and cerebral infarction accompanying hemorrhage, and the dilation of cerebral deep or superficial veins in patients with cerebral venous sinus thrombosis. Moreover, SWI can show the phase contrast between the lesions and the control areas. (authors)

  14. [Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses].

    Science.gov (United States)

    Wechsler, Janine

    2018-02-01

    Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses. Copyright © 2017. Published by Elsevier Masson SAS.

  15. Immune-mediated rippling muscle disease and myasthenia gravis.

    Science.gov (United States)

    Bettini, Mariela; Gonorazky, Hernan; Chaves, Marcelo; Fulgenzi, Ernesto; Figueredo, Alejandra; Christiansen, Silvia; Cristiano, Edgardo; Bertini, Enrico S; Rugiero, Marcelo

    2016-10-15

    Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Cellular immunity and immunopathology in autoimmune Addison's disease.

    Science.gov (United States)

    Bratland, Eirik; Husebye, Eystein S

    2011-04-10

    Autoimmune adrenocortical failure, or Addison's disease, is a prototypical organ-specific autoimmune disorder. In common with related autoimmune endocrinopathies, Addison's disease is only manageable to a certain extent with replacement therapy being the only treatment option. Unfortunately, the available therapy does not restore the physiological hormone levels and biorhythm. The key to progress in treating and preventing autoimmune Addison's disease lies in improving our understanding of the predisposing factors, the mechanisms responsible for the progression of the disease, and the interactions between adrenal antigens and effector cells and molecules of the immune system. The aim of the present review is to summarize the current knowledge on the role of T cells and cellular immunity in the pathogenesis of autoimmune Addison's disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Small and long regulatory RNAs in the immune system and immune diseases

    NARCIS (Netherlands)

    Stachurska, Anna; Zorro, Maria M.; van der Sijde, Marijke R.; Withoff, Sebo

    2014-01-01

    Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation

  18. Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

    Science.gov (United States)

    Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

    2016-04-01

    Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. © International & American Associations for Dental Research 2016.

  19. The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases.

    Science.gov (United States)

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-01-28

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well.

  20. Immune evasion mechanisms of Entamoeba histolytica: progression to disease

    Directory of Open Access Journals (Sweden)

    Sharmin eBegum

    2015-12-01

    Full Text Available Entamoeba histolytica (Eh is a protozoan parasite that infects 10% of the world’s population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  1. Immune Evasion Mechanisms of Entamoeba histolytica: Progression to Disease.

    Science.gov (United States)

    Begum, Sharmin; Quach, Jeanie; Chadee, Kris

    2015-01-01

    Entamoeba histolytica (Eh) is a protozoan parasite that infects 10% of the world's population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO) production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells) that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  2. Gut microbiota, immunity and disease: a complex relationship

    Directory of Open Access Journals (Sweden)

    Michele M Kosiewicz

    2011-09-01

    Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

  3. Comparison of protein profiles of beech bark disease-resistant or beech bark disease-susceptible American beech

    Science.gov (United States)

    Mary E. Mason; Marek Krasowski; Judy Loo; Jennifer. Koch

    2011-01-01

    Proteomic analysis of beech bark proteins from trees resistant and susceptible to beech bark disease (BBD) was conducted. Sixteen trees from eight geographically isolated stands, 10 resistant (healthy) and 6 susceptible (diseased/infested) trees, were studied. The genetic complexity of the sample unit, the sampling across a wide geographic area, and the complexity of...

  4. Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

    Directory of Open Access Journals (Sweden)

    Farhana Khanam

    2015-04-01

    Full Text Available Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains.As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest during acute typhoid fever in adults. We similarly assessed membrane preparation (MP IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years with those seen in older children (6-17 years, adults (18-59 years, and age-matched healthy controls.We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid.This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest

  5. Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection.

    Science.gov (United States)

    Zhu, Junping; Zhang, Tong; Cao, Lina; Li, Aixin; Zheng, Kai; Zhang, Nan; Su, Bin; Chen, Zhiyun; Chen, Ning; Wu, Hao; He, Qiushui

    2017-09-29

    Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.

  6. [Immune response of Hansen's disease. Review].

    Science.gov (United States)

    Rada, Elsa; Aranzazu, Nacarid; Convit, Jacinto

    2009-12-01

    Hansen's disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to "resist" host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen's disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory.

  7. Narcolepsy as an Immune-Mediated Disease

    Directory of Open Access Journals (Sweden)

    Alberto K. De la Herrán-Arita

    2014-01-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA and T cell receptor (TCR polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1 in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

  8. Prevention of edema disease in pigs by passive immunization

    DEFF Research Database (Denmark)

    Johansen, M.; Andresen, Lars Ole; Thomsen, L.K.

    2000-01-01

    The effect of treatment with verotoxin 2e (VT2e) specific antiserum was evaluated in 3 Danish pig herds with edema disease (ED). The antiserum was prepared by immunizing horses with a VT2e toroid. The study was performed as a randomized blind field trial with parallel treatment and control groups...

  9. Polymorphisms of immunity genes and susceptibility to otitis media in children.

    Directory of Open Access Journals (Sweden)

    Johanna Nokso-Koivisto

    Full Text Available Acute otitis media (OM is a common disease which often develops through complex interactions between the host, the pathogen and environmental factors. We studied single nucleotide polymorphisms (SNPs of genes involved in innate and adaptive immunity, and other host and environmental factors for their role in OM.Using Sequenom Massarray platform, 21 SNPs were studied in 653 children from prospective (n = 202 and retrospective (n = 451 cohorts. Data were analyzed for the relationship between SNPs and upper respiratory infection (URI frequency, risk of acute OM during URI episodes, and proneness to recurrent OM.Increased risk for OM proneness was associated with CX3CR1 (Thr280Met SNP and with a jointly interactive group of IL-10 (-1082 SNP, IL-1β (-511 wild type genotype and white race. Family history of OM proneness independently increased the risk for frequent URIs, OM occurrence during URI, and OM proneness. Additionally, IL-1β (-31 SNP was associated with increased risk for frequent URIs, but IL-10 (-592, IL-1β (-511, IL-5 (-746 and IL-8 (-251 SNPs were associated with decreased risk of URI.IL-1β (-31, CX3CR1 (Thr280Met, IL-10 (-1082 and IL-1β (-511 SNPs were associated with increased risk for frequent URIs or OM proneness.

  10. Arthropod Innate Immune Systems and Vector-Borne Diseases

    OpenAIRE

    Baxter, Richard H. G.; Contet, Alicia; Krueger, Kathryn

    2017-01-01

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins ...

  11. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

    OpenAIRE

    Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains deb...

  12. Behcet's disease in acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Beenish Siddiqui

    2016-01-01

    Full Text Available HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.

  13. Severe infectious diseases of childhood as monogenic inborn errors of immunity

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-01-01

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications. PMID:26621750

  14. Severe infectious diseases of childhood as monogenic inborn errors of immunity.

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-12-22

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

  15. The inflammatory bowel disease (IBD susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish

    Directory of Open Access Journals (Sweden)

    Stefan H. Oehlers

    2011-11-01

    Inflammatory bowel disease (IBD, in the form of Crohn’s disease (CD or ulcerative colitis (UC, is a debilitating chronic immune disorder of the intestine. A complex etiology resulting from dysfunctional interactions between the intestinal immune system and its microflora, influenced by host genetic susceptibility, makes disease modeling challenging. Mutations in NOD2 have the highest disease-specific risk association for CD, and a related gene, NOD1, is associated with UC. NOD1 and NOD2 encode intracellular bacterial sensor proteins acting as innate immune triggers, and represent promising therapeutic targets. The zebrafish has the potential to aid in modeling genetic and environmental aspects of IBD pathogenesis. Here, we report the characterization of the Nod signaling components in the zebrafish larval intestine. The nod1 and nod2 genes are expressed in intestinal epithelial cells and neutrophils together with the Nod signaling pathway genes ripk2, a20, aamp, cd147, centaurin b1, erbin and grim-19. Using a zebrafish embryo Salmonella infection model, morpholino-mediated depletion of Nod1 or Nod2 reduced the ability of embryos to control systemic infection. Depletion of Nod1 or Nod2 decreased expression of dual oxidase in the intestinal epithelium and impaired the ability of larvae to reduce intracellular bacterial burden. This work highlights the potential use of zebrafish larvae in the study of components of IBD pathogenesis.

  16. [Environmental pollutants as adjuvant factors of immune system derived diseases].

    Science.gov (United States)

    Lehmann, Irina

    2017-06-01

    The main task of the immune system is to protect the body against invading pathogens. To be able to do so, immune cells must be able to recognize and combat exogenous challenges and at the same time tolerate body-borne structures. A complex regulatory network controls the sensitive balance between defense and tolerance. Perturbation of this network ultimately leads to the development of chronic inflammation, such as allergies, autoimmune reactions, and infections, because the immune system is no longer able to efficiently eliminate invading pathogens. Environmental pollutants can cause such perturbations by affecting the function of immune cells in such a way that they would react hypersensitively against allergens and the body's own structures, respectively, or that they would be no longer able to adequately combat pathogens. This indirect effect is also known as adjuvant effect. For pesticides, heavy metals, wood preservatives, or volatile organic compounds such adjuvant effects are well known. Examples of the mechanism by which environmental toxins contribute to chronic inflammatory diseases are manifold and will be discussed along asthma and allergies.While the immune system of healthy adults is typically well able to distinguish between foreign and endogenous substances even under adverse environmental conditions, that of children would react much more sensible upon comparable environmental challenges. To prevent priming for diseases by environmental cues during that highly sensitive period of early childhood children are to be particularly protected.

  17. Attention deficit hyperactivity disorder may be a highly inflammation and immune-associated disease (Review).

    Science.gov (United States)

    Zhou, Rong-Yi; Wang, Jiao-Jiao; Sun, Ji-Chao; You, Yue; Ying, Jing-Nang; Han, Xin-Min

    2017-10-01

    Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder. Previous research has indicated that genetic factors, family education, environment and dietary habits are associated with ADHD. It has been determined that in China many children with ADHD also have allergic rhinitis or asthma. These children are more susceptible to the common cold or upper respiratory infections compared with normal healthy children. Additionally, the common cold or an upper respiratory infection may lead to disease recurrence or worsen the symptoms in these children. Previous studies have determined that ADHD may have a close association with allergic disease. Based on the clinically observed phenomenon and previous studies, it was hypothesized that ADHD is a high inflammation and immune‑associated disease. Therefore, the authors designed clinical and animal experiments to test this hypothesis in the future. Immune system disorders may be a novel part of the etiology of ADHD. The current report may have implications for future clinical practice.

  18. [Gut microbiota and immune crosstalk in metabolic disease].

    Science.gov (United States)

    Burcelin, Rémy

    2017-01-01

    The aim of the review is to discuss about the role played by the defence crosstalk between the gut microbiota and the intestinal immune system, in the development of metabolic disease focusing on obesity and diabetes. Starting from physiological and pathological stand points and based on the latest published data, this review is addressing how the concept of the hologenome theory of evolution can drive the fate of metabolic disease. The notion of "metabolic infection" to explain the "metabolic inflammation" is discussed. This imply comments about the process of bacterial translocation and impaired intestinal immune defense against commensals. Eventually this review sets the soil for personalized medicine. The monthly increase in the number of publications on the gut microbiota to intestinal immune defense and the control of metabolism demonstrate the importance of this field of investigation. The notion of commensal as "self or non-self" has to be reevaluated in the light of the current data. Furthermore, data demonstrate the major role played by short chain fatty acids, secondary bile acids, LPS, peptidoglycans, indole derivatives, and other bacteria-related molecules on the shaping of cells involved in the intestinal protection against commensals is now becoming a central player in the incidence of metabolic diseases. The literature demonstrates that the onset of metabolic diseases and some specific co-morbidities can be explained by a gut microbiota to intestinal immune system crosstalk. Therefore, one should now consider this avenue of investigation as a putative source of biomarkers and therapeutic targets to personalize the treatment of metabolic disease and its co-morbidities. Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes

  19. Disease susceptibiliy in the zig-zag model of host-microbe Interactions: only a consequence of immune suppression?

    OpenAIRE

    Keller, Harald; Boyer, Laurent; Abad, Pierre

    2016-01-01

    For almost ten years, the Zig-Zag model has provided a convenient framework for explaining the molecular bases of compatibility and incompatibility in plant-microbe interactions (Jones and Dangl, 2006). According to the Zig-Zag model, disease susceptibility is a consequence of the suppression of host immunity during the evolutionary arms race between plants and pathogens. The Zig-Zag model thus fits well with biotrophic interactions, but is less applicable to interactions involving pathogens ...

  20. The role of the local microenvironment in regulating susceptibility and immune responses to sexually transmitted viruses in the female genital tract.

    Science.gov (United States)

    Kaushic, Charu

    2009-12-01

    Sexually transmitted viruses cause chronic infections that have serious long-term health consequences. Based on the evidence from clinical and epidemiological studies, women carry a disproportionately higher burden of sexually transmitted diseases. The reasons for this are not well understood and possibly relate to a variety of social, behavioral and economic factors. In addition to these factors there are biological reasons that contribute to the higher prevalence in women. In this context it is critical to focus on and understand the local microenvironment of the female genital tract, since the majority of viral infections in women occur by heterosexual transmission. The genital tract is also the target site for initiation and maintenance of protective immune responses that could prevent or eliminate viral infections. The epithelial cells of the genital tract provide the first line of defense against viral entry. The interactions between each sexually transmitted virus and the genital epithelium are distinct and determine the outcome of exposure. They are also influenced by a number of factors in the local genital milieu. Among these factors are the female sex hormones that regulate both the susceptibility as well as immune responses to viral infections in the genital tract. Better understanding of the interactions of viruses with the local environment in the female genital tract will lead to development of novel methods to prevent sexually transmitted infections as well as to enhance innate and adaptive immunity.

  1. Ethical issues of genetic susceptibility testing for occupational diseases: opinions of trainees in a high-risk job

    NARCIS (Netherlands)

    Visser, M. J.; Rhebergen, M. D. F.; Kezic, S.; van Dijk, F. J. H.; Willems, D. L.; Verberk, M. M.

    2013-01-01

    Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are

  2. Small and Long Regulatory RNAs in the Immune System and Immune Diseases

    OpenAIRE

    Stachurska, Anna; Zorro, Maria M.; van der Sijde, Marijke R.; Withoff, Sebo

    2014-01-01

    Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs...

  3. Immune responses of poultry to Newcastle disease virus.

    Science.gov (United States)

    Kapczynski, Darrell R; Afonso, Claudio L; Miller, Patti J

    2013-11-01

    Newcastle disease (ND) remains a constant threat to poultry producers worldwide, in spite of the availability and global employment of ND vaccinations since the 1950s. Strains of Newcastle disease virus (NDV) belong to the order Mononegavirales, family Paramyxoviridae, and genus Avulavirus, are contained in one serotype and are also known as avian paramyxovirus serotype-1 (APMV-1). They are pleomorphic in shape and are single-stranded, non-segmented, negative sense RNA viruses. The virus has been reported to infect most orders of birds and thus has a wide host range. Isolates are characterized by virulence in chickens and the presence of basic amino acids at the fusion protein cleavage site. Low virulent NDV typically produce subclinical disease with some morbidity, whereas virulent isolates can result in rapid, high mortality of birds. Virulent NDV are listed pathogens that require immediate notification to the Office of International Epizootics and outbreaks typically result in trade embargos. Protection against NDV is through the use of vaccines generated with low virulent NDV strains. Immunity is derived from neutralizing antibodies formed against the viral hemagglutinin and fusion glycoproteins, which are responsible for attachment and spread of the virus. However, new techniques and technologies have also allowed for more in depth analysis of the innate and cell-mediated immunity of poultry to NDV. Gene profiling experiments have led to the discovery of novel host genes modulated immediately after infection. Differences in virus virulence alter host gene response patterns have been demonstrated. Furthermore, the timing and contributions of cell-mediated immune responses appear to decrease disease and transmission potential. In view of recent reports of vaccine failure from many countries on the ability of classical NDV vaccines to stop spread of disease, renewed interest in a more complete understanding of the global immune response of poultry to NDV will be

  4. Arthropod Innate Immune Systems and Vector-Borne Diseases.

    Science.gov (United States)

    Baxter, Richard H G; Contet, Alicia; Krueger, Kathryn

    2017-02-21

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization, and agglutination. Effector responses are initiated by damage signals such as reactive oxygen species signaling from epithelial cells and recognized by cell surface receptors on hemocytes. Antiviral immunity is primarily mediated by siRNA pathways but coupled with interferon-like signaling, antimicrobial peptides, and thioester-containing proteins. Molecular mechanisms of immunity are closely linked to related traits of longevity and fertility, and arthropods have the capacity for innate immunological memory. Advances in understanding vector immunity can be leveraged to develop novel control strategies for reducing the rate of transmission of both ancient and emerging threats to global health.

  5. SUSCEPTIBILITY TO OZONE-INDUCED INJURY AND ANTIOXIDANT COMPENSATION IN RAT MODELS OF CARDIOVASCULAR DISEASE

    Science.gov (United States)

    Increased oxidative stress and compromised antioxidant status are common pathologic factors of cardiovascular diseases (CVD). It is hypothesized that individuals with chronic CVD are more susceptible to environmental exposures due to underlying oxidative stress. To determine the ...

  6. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus.

    Science.gov (United States)

    Li, Feng-Yen; Chaigne-Delalande, Benjamin; Su, Helen; Uzel, Gulbu; Matthews, Helen; Lenardo, Michael J

    2014-04-03

    Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.

  7. Impact of Bee Venom Enzymes on Diseases and Immune Responses.

    Science.gov (United States)

    Hossen, Md Sakib; Shapla, Ummay Mahfuza; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-12-27

    Bee venom (BV) is used to treat many diseases and exhibits anti-inflammatory, anti-bacterial, antimutagenic, radioprotective, anti-nociceptive immunity promoting, hepatocyte protective and anti-cancer activity. According to the literature, BV contains several enzymes, including phospholipase A2 (PLA2), phospholipase B, hyaluronidase, acid phosphatase and α-glucosidase. Recent studies have also reported the detection of different classes of enzymes in BV, including esterases, proteases and peptidases, protease inhibitors and other important enzymes involved in carbohydrate metabolism. Nevertheless, the physiochemical properties and functions of each enzyme class and their mechanisms remain unclear. Various pharmacotherapeutic effects of some of the BV enzymes have been reported in several studies. At present, ongoing research aims to characterize each enzyme and elucidate their specific biological roles. This review gathers all the current knowledge on BV enzymes and their specific mechanisms in regulating various immune responses and physiological changes to provide a basis for future therapies for various diseases.

  8. Impact of Bee Venom Enzymes on Diseases and Immune Responses

    Directory of Open Access Journals (Sweden)

    Md. Sakib Hossen

    2016-12-01

    Full Text Available Bee venom (BV is used to treat many diseases and exhibits anti-inflammatory, anti-bacterial, antimutagenic, radioprotective, anti-nociceptive immunity promoting, hepatocyte protective and anti-cancer activity. According to the literature, BV contains several enzymes, including phospholipase A2 (PLA2, phospholipase B, hyaluronidase, acid phosphatase and α-glucosidase. Recent studies have also reported the detection of different classes of enzymes in BV, including esterases, proteases and peptidases, protease inhibitors and other important enzymes involved in carbohydrate metabolism. Nevertheless, the physiochemical properties and functions of each enzyme class and their mechanisms remain unclear. Various pharmacotherapeutic effects of some of the BV enzymes have been reported in several studies. At present, ongoing research aims to characterize each enzyme and elucidate their specific biological roles. This review gathers all the current knowledge on BV enzymes and their specific mechanisms in regulating various immune responses and physiological changes to provide a basis for future therapies for various diseases.

  9. Early Nutrition as a Major Determinant of 'Immune Health': Implications for Allergy, Obesity and Other Noncommunicable Diseases.

    Science.gov (United States)

    Prescott, Susan L

    2016-01-01

    Early-life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. Dietary changes are at the center of the emerging epigenetic paradigms that underpin the rise in many modern inflammatory and metabolic diseases. There is growing evidence that exposures in pregnancy and the early postnatal period can modify gene expression and disease susceptibility. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients. Oligosaccharides (soluble fiber), antioxidants, polyunsaturated fatty acids, folate and other vitamins have documented effects on immune function as well as metabolism. Some have also been implicated in modified risk of allergic diseases in observational studies. Intervention studies are largely limited to trials with polyunsaturated fatty acids and oligosaccharides, showing preliminary but yet unconfirmed benefits in allergy prevention. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programming is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While an epigenetic mechanism provides a strong explanation of how nutritional exposures can affect fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function--including diet-induced changes in the microbiome. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures early in life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the

  10. Verneuil's disease, innate immunity and vitamin D: a pilot study.

    Science.gov (United States)

    Guillet, A; Brocard, A; Bach Ngohou, K; Graveline, N; Leloup, A-G; Ali, D; Nguyen, J-M; Loirat, M-J; Chevalier, C; Khammari, A; Dreno, B

    2015-07-01

    Verneuil's disease is a chronic inflammatory skin disease of the follicles in apocrine glands rich area of the skin (axillary, inguinal, anogenital) and is associated with a deficient skin innate immunity. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. Recently, vitamin D has been shown to stimulate skin innate immunity. The primary objective of the study was to assess whether Verneuil's disease was associated with vitamin D deficiency. The secondary objective was to determine whether vitamin D supplementation could improve inflammatory lesions. First, 25(OH) vitamin D3 serum levels in patients with Verneuil's disease followed at Nantes University Hospital were compared to those of healthy donors from the French Blood Bank. Then, a pilot study was conducted in 14 patients supplemented with vitamin D according to their vitamin D level at baseline at months 3 and 6. The endpoints at 6 months were decreased by at least 20% in the number of nodules and in the frequency of flare-ups. Twenty-two patients (100%) had vitamin D deficiency (level vitamin D deficiency (91%) of whom 14% were severely deficient. In 14 patients, the supplementation significantly decreased the number of nodules at 6 months (P = 0.01133), and the endpoints were achieved in 79% of these patients. A correlation between the therapeutic success and the importance of the increase in vitamin D level after supplementation was observed (P = 0.01099). Our study shows that Verneuil's disease is associated with a major vitamin D deficiency, correlated with the disease severity. It suggests that vitamin D could significantly improve the inflammatory nodules, probably by stimulating the skin innate immunity. A larger randomized study is needed to confirm these findings. © 2014 European Academy of Dermatology and Venereology.

  11. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

    NARCIS (Netherlands)

    Tsoi, Lam C.; Spain, Sarah L.; Knight, Jo; Ellinghaus, Eva; Stuart, Philip E.; Capon, Francesca; Ding, Jun; Li, Yanming; Tejasvi, Trilokraj; Gudjonsson, Johann E.; Kang, Hyun M.; Allen, Michael H.; McManus, Ross; Novelli, Giuseppe; Samuelsson, Lena; Schalkwijk, Joost; Stahle, Mona; Burden, A. David; Smith, Catherine H.; Cork, Michael J.; Estivill, Xavier; Bowcock, Anne M.; Krueger, Gerald G.; Weger, Wolfgang; Worthington, Jane; Tazi-Ahnini, Rachid; Nestle, Frank O.; Hayday, Adrian; Hoffmann, Per; Winkelmann, Juliane; Wijmenga, Cisca; Langford, Cordelia; Edkins, Sarah; Andrews, Robert; Blackburn, Hannah; Strange, Amy; Band, Gavin; Pearson, Richard D.; Vukcevic, Damjan; Spencer, Chris C. A.; Deloukas, Panos; Mrowietz, Ulrich; Schreiber, Stefan; Weidinger, Stephan; Koks, Sulev; Kingo, Kuelli; Esko, Tonu; Metspalu, Andres; Ricaño Ponce, Isis; Trynka, Gosia

    2012-01-01

    To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36

  12. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

    NARCIS (Netherlands)

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B.; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J.; Yeung, Rae S. M.; Tan, Dennis E. K.; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C.; Burgner, David; Kuijpers, Taco W.; Hibberd, Martin L.; Lau, Yu-Lung; Zhang, Jing; Ma, Xiao-Jing; Liu, Fang; Wu, Lin; Yoo, Jeong-Jin; Hong, Soo-Jong; Kim, Kwi-Joo; Kim, Jae-Jung; Park, Young-Mi; Mi Hong, Young; Sohn, Sejung; Young Jang, Gi; Ha, Kee-Soo; Nam, Hyo-Kyoung; Byeon, Jung-Hye; Weon Yun, Sin; Ki Han, Myung; Lee, Kyung-Yil; Hwang, Ja-Young; Kuipers, Irene M.; Ottenkamp, Jaap J.; Biezeveld, Maarten; Tacke, Carline

    2011-01-01

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from

  13. Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches.

    Science.gov (United States)

    Penêda, José Ferreira; Lima, Nuno Barros; Monteiro, Francisco; Silva, Joana Vilela; Gama, Rita; Condé, Artur

    2018-03-07

    Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. A review of articles on IMIED from the last 10 years was conducted using PubMed ® database. IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Detection and Characterization of Infections and Infection Susceptibility

    Science.gov (United States)

    2018-03-27

    Immune Disorders; Chronic Granulomatous Disease; Genetic Immunological Deficiencies; Hyperimmunoglobulin-E Recurrent Infection Syndrome; Recurrent Infections; Unknown Immune Deficiency; GATA2 Deficiency (MonoMAC); Nontuberculous Mycobacterial Infections; Hyper IgE (Job s) Syndrome; Leukocyte Adhesion Deficiency; Susceptibility to Disseminated Infections; Primary Immune Deficiency Disease (PIDD)

  15. Gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs.

    Science.gov (United States)

    Cizauskas, Carrie A; Turner, Wendy C; Wagner, Bettina; Küsters, Martina; Vance, Russell E; Getz, Wayne M

    2014-11-12

    Most vertebrates experience coinfections, and many pathogen-pathogen interactions occur indirectly through the host immune system. These interactions are particularly strong in mixed micro-macroparasite infections because of immunomodulatory effects of helminth parasites. While these trade-offs have been examined extensively in laboratory animals, few studies have examined them in natural systems. Additionally, many wildlife pathogens fluctuate seasonally, at least partly due to seasonal host immune changes. We therefore examined seasonality of immune resource allocation, pathogen abundance and exposure, and interactions between infections and immunity in plains zebra (Equus quagga) in Etosha National Park (ENP), Namibia, a system with strongly seasonal patterns of gastrointestinal (GI) helminth infection intensity and concurrent anthrax outbreaks. Both pathogens are environmentally transmitted, and helminth seasonality is driven by environmental pressures on free living life stages. The reasons behind anthrax seasonality are currently not understood, though anthrax is less likely directly driven by environmental factors. We measured a complex, interacting set of variables and found evidence that GI helminth infection intensities, eosinophil counts, IgE and IgGb antibody titers, and possibly IL-4 cytokine signaling were increased in wetter seasons, and that ectoparasite infestations and possibly IFN-γ cytokine signaling were increased in drier seasons. Monocyte counts and anti-anthrax antibody titers were negatively associated with wet season eosinophilia, and monocytes were negatively correlated with IgGb and IgE titers. Taken together, this supports the hypothesis that ENP wet seasons are characterized by immune resource allocation toward Th-2 type responses, while Th1-type immunity may prevail in drier seasons, and that hosts may experience Th1-Th2 trade-offs. We found evidence that this Th2-type resource allocation is likely driven by GI parasite infections

  16. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  17. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Lesley Jones

    2010-11-01

    Full Text Available Late Onset Alzheimer's disease (LOAD is the leading cause of dementia. Recent large genome-wide association studies (GWAS identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

  18. Convergent genetic and expression data implicate immunity in Alzheimer's disease.

    Science.gov (United States)

    2015-06-01

    Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. Copyright © 2015. Published by Elsevier Inc.

  19. Immune and biochemical responses in skin differ between bovine hosts genetically susceptible and resistant to the cattle tick Rhipicephalus microplus.

    Science.gov (United States)

    Franzin, Alessandra Mara; Maruyama, Sandra Regina; Garcia, Gustavo Rocha; Oliveira, Rosane Pereira; Ribeiro, José Marcos Chaves; Bishop, Richard; Maia, Antônio Augusto Mendes; Moré, Daniela Dantas; Ferreira, Beatriz Rossetti; Santos, Isabel Kinney Ferreira de Miranda

    2017-01-31

    abundant in larval and in nymphal salivary glands from ticks feeding on susceptible bovines. Compared with tick-susceptible hosts, genes encoding enzymes producing volatile compounds exhibit significantly lower expression in resistant hosts, which may render them less attractive to larvae; resistant hosts expose ticks to an earlier inflammatory response, which in ticks is associated with significantly lower expression of genes encoding salivary proteins that suppress host immunity, inflammation and coagulation.

  20. Susceptibility, likelihood to be diagnosed, worry and fear for contracting Lyme disease.

    Science.gov (United States)

    Fogel, Joshua; Chawla, Gurasees S

    Risk perception and psychological concerns are relevant for understanding how people view Lyme disease. This study investigates the four separate outcomes of susceptibility, likelihood to be diagnosed, worry, and fear for contracting Lyme disease. University students (n=713) were surveyed about demographics, perceived health, Lyme disease knowledge, Lyme disease preventive behaviors, Lyme disease history, and Lyme disease miscellaneous variables. We found that women were associated with increased susceptibility and fear. Asian/Asian-American race/ethnicity was associated with increased worry and fear. Perceived good health was associated with increased likelihood to be diagnosed, worry, and fear. Correct knowledge was associated with increased susceptibility and likelihood to be diagnosed. Those who typically spend a lot of time outdoors were associated with increased susceptibility, likelihood to be diagnosed, worry, and fear. In conclusion, healthcare providers and public health campaigns should address susceptibility, likelihood to be diagnosed, worry, and fear about Lyme disease, and should particularly target women and Asians/Asian-Americans to address any possible misconceptions and/or offer effective coping strategies. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  1. The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop

    Directory of Open Access Journals (Sweden)

    D. Pagliari

    2015-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

  2. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    P.J. Basso

    2014-09-01

    Full Text Available Inflammatory bowel disease (IBD, which includes Crohn's disease (CD and ulcerative colitis (UC, is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

  3. Shared genetics in coeliac disease and other immune-mediated diseases

    NARCIS (Netherlands)

    Gutierrez-Achury, J.; Coutinho de Almeida, R.; Wijmenga, C.

    Gutierrez-Achury J, Coutinho de Almeida R, Wijmenga C (University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands; University of Brasilia School of Health Sciences, Brasilia, DF, Brazil). Shared genetics in coeliac disease and other immune-mediated diseases

  4. Physiological and pathological adaptations in dairy cows that may increase susceptibility to periparturient diseases and disorders

    Directory of Open Access Journals (Sweden)

    Juan J. Loor

    2010-01-01

    Full Text Available Dairy cows undergo tremendous metabolic and physiological adaptations around parturition to support lactation. The liver  is central to many of these processes, including gluconeogenesis and metabolism of fatty acids mobilized from adipose tis-  sue. Fat accumulation may impair normal functions of the liver and increase ketogenesis, which in turn may predispose cows  to other metabolic abnormalities. Several aspects of dietary management and body condition may alter these adaptations,  affect dry matter intake, and increase or decrease susceptibility to periparturient health problems. Overfeeding energy dur-  ing the dry period is a prominent risk factor. Considerable progress has been made in recent years in describing the adap-  tive changes in the liver and other organs in normal and abnormal states, but this knowledge has not yet identified unequiv-  ocally the key steps that might be compromised during development of metabolic disorders. The potential role of signaling  compounds, such as the inflammatory cytokines released in response to environmental stressors, infectious challenge, and  oxidative stress, in the pathogenesis of periparturient disease is under investigation. New techniques such as functional  genomics, using cDNA or oligonucleotide microarrays, as well as proteomics and metabolomics, provide additional high-  throughput tools to determine the effects of nutrition, management, or stressors on tissue function in development of dis-  ease. Integrative approaches should be fruitful in unraveling the complex interactions of metabolism, immune activation,  stress physiology, and endocrinology that likely underlie development of periparturient disease

  5. Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis

    NARCIS (Netherlands)

    Kavelaars, A; Heijnen, CJ; Tennekes, R; Bruggink, JE; Koolhaas, JM

    1999-01-01

    Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to:reactivity in the hypothalamo-pituitary-adrenal axis.

  6. Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

    Directory of Open Access Journals (Sweden)

    Deanna L. Gibson

    2012-08-01

    Full Text Available The gastrointestinal (GI microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.

  7. Reuma.pt contribution to the knowledge of immune-mediated systemic rheumatic diseases.

    Science.gov (United States)

    Santos, Maria José; Canhão, Helena; Mourão, Ana Filipa; Oliveira Ramos, Filipa; Ponte, Cristina; Duarte, Cátia; Barcelos, Anabela; Martins, Fernando; Melo Gomes, José António

    2017-01-01

    Patient registries are key instruments aimed at a better understanding of the natural history of diseases, at assessing the effectiveness of therapeutic interventions, as well as identifying rare events or outcomes that are not captured in clinical trials. However, the potential of registries goes far beyond these aspects. For example, registries promote the standardization of clinical practice, can also provide information on domains that are not routinely collected in clinical practice and can support decision-making. Being aware of the importance of registries, the Portuguese Society of Rheumatology developed the Rheumatic Diseases Portuguese Register- Reuma.pt - which proved to be an innovative instrument essential to a better understanding of systemic immune-mediated rheumatic diseases. To describe the contribution of Reuma.pt to the knowledge of systemic immune-mediated rheumatic diseases. Reuma.pt is widely implemented, with 77 centres actively contributing to the recruitment and follow-up of patients. Reuma.pt follows in a standardized way patients with the following systemic inflammatory rheumatic diseases: rheumatoid arthritis (n=6218), psoriatic arthritis (n=1498), spondyloarthritis (n=2529), juvenile idiopathic arthritis (n =1561), autoinflammatory syndromes (n=122), systemic lupus erythematosus (n =1718), systemic sclerosis (n=180) and vasculitis (n=221). This platform is intended for use as an electronic medical record, provides standardized assessment of patients and support to the clinical decision, thereby contributing to a better quality of care of rheumatic patients. The research based on Reuma.pt identified genetic determinants of susceptibility and response to therapy, characterized in detail systemic rheumatic diseases and their long-term impact, critically appraised the performance of instruments for monitoring the disease activity, established the effectiveness and safety of biologic therapies and identified predictors of response, and

  8. Exploration of genetic susceptibility factors for Parkinson's disease ...

    Indian Academy of Sciences (India)

    1Neurosciences Research Group, School of Medicine and Institute of Genetics, Universidad Nacional de Colombia, Bogotá ... factors for Parkinson's disease in a South American sample. J. Genet. 89, ... In the current work, we report the results of a system- ..... Synaptic dysfunction and oxidative stress in Alzheimer's disease:.

  9. Cesarean section and disease associated with immune function

    DEFF Research Database (Denmark)

    Kristensen, Kim; Henriksen, Lonny

    2016-01-01

    colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma. CONCLUSION: Children delivered by CS are at increased......BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought...... to further explore these associations using discrimination between the effects of acute versus elective CS. METHODS: We performed a population- and national register-based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated...

  10. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap.

    Science.gov (United States)

    Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 10(9)/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave's disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave's disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy.

  11. Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease

    OpenAIRE

    Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter Alan; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L.; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A.; Naj, Adam C.; Sims, Rebecca

    2014-01-01

    PUBLISHED BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over...

  12. Susceptibility and Immune Defence Mechanisms of Rhynchophorus ferrugineus (Olivier (Coleoptera: Curculionidae against Entomopathogenic Fungal Infections

    Directory of Open Access Journals (Sweden)

    Abid Hussain

    2016-09-01

    Full Text Available Insects infected with entomopathogenic fungi, experience physiological changes that influence their growth and immune defence. The potential of nine isolates of entomopathogenic fungi was evaluated after determining percent germination and relative conidial hydrophobicity. However, nutritional indices were evaluated after immersing eighth-instar Rhynchophorus ferrugineus larvae into each isolate suspension (1 × 107 conidia/mL. The results showed that isolates B6884 and M9374 had 44.51% and 39.02% higher conidial hydrophobicity compared with isolate I03011 (least virulent. The results of nutritional index assays revealed a significant reduction in growth indices after infection with different isolates. Compared with control, B6884 and M9374 greatly decreased larval growth by reducing the efficacy of conversion of ingested food (36%–47% and Efficacy of conversion of digested food (50%–63%. Furthermore, only isolate B6884 induced 100% mortality within 12 days. Compared with control, isolate I03011, possessing the lowest conidial hydrophobicity, only reduced 0.29% of the efficacy of conversion of ingested food (ECI and 0.48% of the efficacy of conversion of digested food (ECD. Similarly, transcriptomic analysis of genes related to the Red palm weevil (RPW immune response, including pathogen recognition receptors (C-type lectin and endo-beta-1,4-glucanse, signal modulator (Serine protease-like protein, signal transductors (Calmodulin-like protein and EF-hand domain containing protein and effectors (C-type lysozyme, Cathepsin L., Defensin-like protein, Serine carboxypeptidase, and Thaumatin-like protein, was significantly increased in larval samples infected with B6884 and M9374. These results suggest that for an isolate to be virulent, conidial hydrophobicity and germination should also be considered during pathogen selection, as these factors could significantly impact host growth and immune defence mechanisms.

  13. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio

    2010-01-01

    BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype...... of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3...... of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider...

  14. Cardiovascular Disease Susceptibility and Resistance in Circumpolar Inuit Populations

    DEFF Research Database (Denmark)

    Tvermosegaard, Maria; Dahl-Petersen, Inger K; Nielsen, Nina Odgaard

    2015-01-01

    Cardiovascular disease (CVD) is a major public health issue in indigenous populations in the Arctic. These diseases have emerged concomitantly with profound social changes over the past 60 years. The aim of this study was to summarize the literature on CVD risk among Arctic Inuit. Literature...... on prevalence, incidence, and time trends for CVD and its risk factors in Arctic Inuit populations was reviewed. Most evidence supports a similar incidence of coronary heart disease and a higher incidence of cerebrovascular disease among Arctic Inuit than seen in western populations. Factors that may increase...... intake (at least documented in Greenland), and contaminant levels are declining. Although there have been marked socioeconomic and dietary changes, it remains unsolved and to some extent controversial how this may have influenced cardiovascular risk among Arctic Inuit. The increase in life expectancy...

  15. Bipolar disorder: idioms of susceptibility and disease and the role of 'genes' in illness explanations.

    Science.gov (United States)

    Baart, Ingrid; Widdershoven, Guy

    2013-11-01

    This qualitative study explores (1) how members of the Dutch Association for People with Bipolar Disorder explain the affliction of bipolar disorder; (2) the relationship between genetic, environmental and personal factors in these explanations and (3) the relationship between illness explanations, self-management and identity. A total of 40 participants took part in seven different focus group discussions. The results demonstrate that there are two different explanatory idioms, each one centred around an opposing concept, that is, susceptibility and disease. Individuals who construct explanations around the concept of 'disease' attach more importance to 'genes and chemicals' than to environmental components in the onset of the disorder, whereas individuals adhering to the central concept of 'susceptibility' tend to do this much less. Compared with individuals using the 'susceptibility' idiom, those who use a 'disease' idiom tend to observe fewer possibilities for self-management and are less inclined to construct normalcy through a quest for personal growth. Stories of suffering seem more integral to the 'disease' idiom than to the 'susceptibility' idiom. The 'disease' idiom seems less integrated in a contemporary surveillance psychiatric discourse than the 'susceptibility' idiom; however, both vocabularies can offer normative constraints.

  16. Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.

    Science.gov (United States)

    Miyoshi, Jun; Bobe, Alexandria M; Miyoshi, Sawako; Huang, Yong; Hubert, Nathaniel; Delmont, Tom O; Eren, A Murat; Leone, Vanessa; Chang, Eugene B

    2017-07-11

    Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    Science.gov (United States)

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

  18. Genetic prion disease: no role for the immune system in disease pathogenesis?

    Science.gov (United States)

    Friedman-Levi, Yael; Binyamin, Orli; Frid, Kati; Ovadia, Haim; Gabizon, Ruth

    2014-08-01

    Prion diseases, which can manifest by transmissible, sporadic or genetic etiologies, share several common features, such as a fatal neurodegenerative outcome and the aberrant accumulation of proteinase K (PK)-resistant PrP forms in the CNS. In infectious prion diseases, such as scrapie in mice, prions first replicate in immune organs, then invade the CNS via ascending peripheral tracts, finally causing death. Accelerated neuroinvasion and death occurs when activated prion-infected immune cells infiltrate into the CNS, as is the case for scrapie-infected mice induced for experimental autoimmune encephalomyelitis (EAE), a CNS inflammatory insult. To establish whether the immune system plays such a central role also in genetic prion diseases, we induced EAE in TgMHu2ME199K mice, a line mimicking for late onset genetic Creutzfeldt Jacob disease (gCJD), a human prion disease. We show here that EAE induction of TgMHu2ME199K mice neither accelerated nor aggravated prion disease manifestation. Concomitantly, we present evidence that PK-resistant PrP forms were absent from CNS immune infiltrates, and most surprisingly also from lymph nodes and spleens of TgMHu2ME199K mice at all ages and stages of disease. These results imply that the mechanism of genetic prion disease differs widely from that of the infectious presentation, and that the conversion of mutant PrPs into PK resistant forms occurs mostly/only in the CNS. If the absence of pathogenic PrP forms form immune organs is also true for gCJD patients, it may suggest their blood is devoid of prion infectivity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

    Science.gov (United States)

    Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

    2012-01-01

    Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

  20. The Immune System: Basis of so much Health and Disease: 4. Immunocytes.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-05-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers cells of the immune system (immunocytes). Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  1. Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.

    Science.gov (United States)

    Andersson, I M; Lorentzen, J C; Ericsson-Dahlstrand, A

    2000-11-01

    Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine-immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation-susceptible Dark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1-30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, beta-glucan-challenged DA rats responded with an aggravated arthritic process, indicating an anti-inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan-challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone-independent mechanisms. In conclusion, the hypothalamic-pituitary-adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal

  2. Developmental origin of immune diseases-Environmental influences

    DEFF Research Database (Denmark)

    Strom, M.; Halldorsson, T. I.; Hansen, S.

    2015-01-01

    (PCBs), organochlorine pesticides, andmorerecently perfluoroalkyl substances (PFAS). Developmental exposures to PCBs have, for example, been associated with both otitis media and lower respiratory infections. Evidence regarding asthma and allergic disease is less well established, partly due to lack......Experimental studies have shown that developmental exposures to environmental chemicals may have long lasting adverse consequences for the development of the immune system. In humans such findings have mostly been explored for persistent organic pollutants (POPs) including polychlorinated biphenyls...... years of age we have examined the long term consequences of in utero exposure to POPs on offspring use of asthma medication and biomarkers of allergic airway disease. Using registry based information on offspring use of asthma medication until 20 years of age, prenatal exposures to PCB-118...

  3. The SPINK gene family and celiac disease susceptibility

    NARCIS (Netherlands)

    Wapenaar, M.C.; Monsuur, A.J.; Poell, J.; Slot, R. van 't; Meijer, J.W.R.; Meijer, G.A.; Mulder, C.J.; Mearin, M.L.; Wijmenga, C.

    2007-01-01

    The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

  4. The SPINK gene family and celiac disease susceptibility

    NARCIS (Netherlands)

    Wapenaar, Martin C.; Monsuur, Alienke J.; Poell, Jos; Slot, Ruben Van 't; Meijer, Jos W. R.; Meijer, Gerrit A.; Mulder, Chris J.; Mearin, Maria Luisa; Wijmenga, Cisca

    The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was

  5. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio

    2010-01-01

    be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count...

  6. Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

    DEFF Research Database (Denmark)

    Siggers, Richard H.; Siggers, Jayda; Thymann, Thomas

    2011-01-01

    on the nutritional, microbial and immunological interactions during the early feeding-induced mucosal dysfunction and later NEC development. We show that introduction of suboptimal enteral formula diets, coupled with parenteral nutrition, predispose to disease, while advancing amounts of mother's milk from birth...... (particularly colostrum) protects against disease. Hence, the transition from parenteral to enteral nutrition shortly after birth plays a pivotal role to secure gut growth, digestive maturation and an appropriate response to bacterial colonization in the sensitive gut of preterm neonates.......The gastrointestinal inflammatory disorder, necrotizing enterocolitis (NEC), is among the most serious diseases for preterm neonates. Nutritional, microbiological and immunological dysfunctions all play a role in disease progression but the relationship among these determinants is not understood...

  7. Degree of host susceptibility in the initial disease outbreak influences subsequent epidemic spread

    Science.gov (United States)

    Severns, Paul M.; Estep, Laura K.; Sackett, Kathryn E.; Mundt, Christopher C.

    2014-01-01

    Summary Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population

  8. The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility

    Science.gov (United States)

    Tong, Xiang; Ma, Yao; Niu, Xundong; Yan, Zhipeng; Liu, Sitong; Peng, Bo; Peng, Shifeng; Fan, Hong

    2016-01-01

    Abstract Objective: The butyrophilin-like 2 (BTNL2) G16071A gene polymorphism has been implicated in the susceptibility to granulomatous diseases, but the results were inconclusive. The objective of the current study was to precisely explore the relationship between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility by the meta-analysis including false-positive report probability (FPRP) test. Methods: A systematic literature search in the PubMed, Embase, and Wanfang databases, China National Knowledge Internet, and commercial Internet search engines was conducted to identify studies published up to April 1, 2016. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the effect size. Statistical analysis was conducted using the STATA 12.0 software and FPRP test sheet. Results: In total, all 4324 cases and 4386 controls from 14 eligible studies were included in the current meta-analysis. By the overall meta-analysis, we found a significant association between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility (A vs G: OR = 1.25, 95% CI = 1.07–1.45, P = 0.005). The meta-regression analyses showed that a large proportion of the between-study heterogeneity was significantly attributed to the ethnicity (A vs G, P = 0.013) and the types of granulomatous diseases (A vs G, P = 0.002). By the subgroup meta-analysis, the BTNL2 G16071A gene polymorphism was associated with granulomatous disease susceptibility in Caucasians (A vs G: OR = 1.37, 95% CI = 1.18–1.58, P susceptibility (A vs G: OR = 1.52, 95% CI = 1.39–1.66, P susceptibility (A vs G, FPRP susceptibility among Caucasians (A vs G, FPRP susceptibility, especially increasing the sarcoidosis susceptibility. In addition, the polymorphism may be greatly associated with likelihood of granulomatous diseases among Caucasians. PMID:27472712

  9. Mannose-Binding Lectin Gene, MBL2, Polymorphisms Do Not Increase Susceptibility to Invasive Meningococcal Disease in a Population of Danish Children

    DEFF Research Database (Denmark)

    Lundbo, Lene F; Sørensen, Henrik T.; Clausen, Louise Nygaard

    2015-01-01

    of the innate immune system may predispose to invasive meningococcal disease (IMD). In this study, we investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, and its promoter on susceptibility to IMD and IMD-associated mortality among children. Methods.  Children (...Background.  Neisseria meningitidis is the cause of meningococcal bacteremia and meningitis, and nasopharyngeal colonization with this pathogen is common. The incidence of invasive disease is highest in infants, whereas adolescents more often are carriers. Altered regulation or dysfunction...

  10. The role of the immune system in Alzheimer disease: Etiology and treatment.

    Science.gov (United States)

    Jevtic, Stefan; Sengar, Ameet S; Salter, Michael W; McLaurin, JoAnne

    2017-11-01

    The immune system is now considered a major factor in Alzheimer Disease (AD). This review seeks to demonstrate how various aspects of the immune system, both in the brain and peripherally, interact to contribute to AD. We highlight classical nervous system immune components, such as complement and microglia, as well as novel aspects of the peripheral immune system that can influence disease, such as monocytes and lymphocytes. By detailing the roles of various immune cells in AD, we summarize an emerging perspective for disease etiology and future therapeutic targets. Copyright © 2017. Published by Elsevier B.V.

  11. Single event upset susceptibilities of latchup immune CMOS process programmable gate arrays

    Science.gov (United States)

    Koga, R.; Crain, W. R.; Crawford, K. B.; Hansel, S. J.; Lau, D. D.; Tsubota, T. K.

    Single event upsets (SEU) and latchup susceptibilities of complementary metal oxide semiconductor programmable gate arrays (CMOS PPGA's) were measured at the Lawrence Berkeley Laboratory 88-in. cyclotron facility with Xe (603 MeV), Cu (290 MeV), and Ar (180 MeV) ion beams. The PPGA devices tested were those which may be used in space. Most of the SEU measurements were taken with a newly constructed tester called the Bus Access Storage and Comparison System (BASACS) operating via a Macintosh II computer. When BASACS finds that an output does not match a prerecorded pattern, the state of all outputs, position in the test cycle, and other necessary information is transmitted and stored in the Macintosh. The upset rate was kept between 1 and 3 per second. After a sufficient number of errors are stored, the test is stopped and the total fluence of particles and total errors are recorded. The device power supply current was closely monitored to check for occurrence of latchup. Results of the tests are presented, indicating that some of the PPGA's are good candidates for selected space applications.

  12. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  14. The Innate Immune System in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Allal Boutajangout

    2013-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloid β (Aβ peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT. Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4 (Potter and Wisniewski (2012, and Verghese et al. (2011. Recently, it has been reported by two groups independently that a rare functional variant (R47H of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs and are the resident macrophages of the central nervous system (CNS. In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

  15. Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

    Directory of Open Access Journals (Sweden)

    Johansson Ingegerd

    2007-06-01

    susceptibility protein.

  16. TGF-b2 induction regulates invasiveness of Theileria-transformed leukocytes and disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Marie Chaussepied

    2010-11-01

    Full Text Available Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva, or tropical theileriosis (T. annulata. Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK. We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence.

  17. Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis

    Science.gov (United States)

    Hinks, Anne; Eyre, Steve; Ke, Xiayi; Barton, Anne; Martin, Paul; Flynn, Edward; Packham, Jon; Worthington, Jane; Thomson, Wendy

    2010-01-01

    Background Genome-wide association studies (GWAS) have been extremely successful in the search for susceptibility risk factors for complex genetic autoimmune diseases. As more studies are published, evidence is emerging of considerable overlap of loci between these diseases. In juvenile idiopathic arthritis (JIA), another complex genetic autoimmune disease, the strategy of using information from autoimmune disease GWAS or candidate gene studies to help in the search for novel JIA susceptibility loci has been successful, with confirmed association with two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features with JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci. Objective To determine the overlap of disease susceptibility loci for RA and JIA. Methods Fifteen single nucleotide polymorphisms (SNPs) at nine RA-associated loci were genotyped in Caucasian patients with JIA (n=1054) and controls (n=3531) and tested for association with JIA. Allele and genotype frequencies were compared between cases and controls using the genetic analysis software, PLINK. Results Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA. Weak evidence of association of JIA with three additional loci (Chr6q23, KIF5A and PRKCQ) was also obtained, which warrants further investigation. Conclusion All these loci are good candidates in view of the known pathogenesis of JIA, as genes within these regions (TRAF1, STAT4, TNFAIP3, PRKCQ) are known to be involved in T-cell receptor signalling or activation pathways. PMID:19674979

  18. The Effect of Tsukamurella inchonensis Bacterin on the Immune Response Against Influenza and Newcastle Disease Vaccines in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Forough Talazadeh

    2016-11-01

    Full Text Available Background: In poultry production, improving immunity is very important to prevent infectious diseases. One solution to improve the immunity of animals and to decrease their susceptibility to infectious disease is administration of immunostimulants. Surveys have indicated that some bacteria can work as immunomodulators such as Mycobacterium vaccae and can promote Th1-mediated mechanisms, and switch off pre-existing Th2 preponderance (1. Objectives: The aim of this study was to examine the effect of Tsukamurella inchonensis bacterin on the immune response against Influenza and Newcastle disease vaccine in broiler chickens . Materials and Methods: A total of 170 day-old broiler chicks were purchased and divided randomly into 5 equal groups. Chickens of group A received 106 bacterin subcutaneously on two days before vaccination against Newcastle disease and avian influenza. Chickens of group B received 106 bacterin subcutaneously on six days after the first injection of bacterin. Chickens of group C received 106bacterin subcutaneously on six days after the second injection of bacterin. Chickens of group D, vaccinated against Newcastle disease and avian influenza but did not receive bacterin. Chickens of group E, did not vaccinate against Newcastle disease and avian influenza and did not receive bacterin. All groups except group E, were vaccinated with live Newcastle vaccine and AI-ND killed vaccine (subtype H9N2. Blood samples were collected and antibody titer against Newcastle disease vaccine and avian influenza vaccine was determined by HI test. Results: The results of present study showed that receiving of Tsukamurella inchonensis bacterin for 3 times, significantly increased the specific antibody response to avian influenza subtype H9N2 vaccine. Also about Newcastle vaccine, significantly increased the specific antibody response to Newcastle vaccine at 21 and 28 days after vaccination. Conclusions: Receiving of Tsukamurella inchonensis bacterin

  19. Impact of Maternal Exercise during Pregnancy on Offspring Chronic Disease Susceptibility.

    Science.gov (United States)

    Blaize, A Nicole; Pearson, Kevin J; Newcomer, Sean C

    2015-10-01

    Maternal behaviors during pregnancy have been reported to impact offspring health in adulthood. In this article we explore the novel hypothesis that exercise during pregnancy can protect against chronic disease susceptibility in the offspring. To date, research has demonstrated that improvements in metabolic outcomes, cardiovascular risk, and cancer can occur in response to maternal exercise during pregnancy.

  20. The innate immune signaling in cancer and cardiometabolic diseases: Friends or foes?

    Science.gov (United States)

    Wang, Weijun; Zhang, Yaxing; Yang, Ling; Li, Hongliang

    2017-02-28

    The innate immune system is responsible for sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) by several types of germline-encoded pattern-recognition receptors (PRRs). It has the capacity to help the human body maintain homeostasis under normal conditions. However, in pathological conditions, PAMPs or DAMPs trigger aberrant innate immune and inflammatory responses and thus negatively or positively influence the progression of cancer and cardiometabolic diseases. Interestingly, we found that some elements of innate immune signaling are involved in these diseases partially via immune-independent manners, indicating a deeper understanding of the function of innate immune signaling in these diseases is urgent. In this review, we summarize the primary innate immune signaling pathways and their association with cancer and cardiometabolic diseases, with the aim of providing effective therapies for these diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Mycobacterium abscessus subsp. abscessus Lung Disease: Drug Susceptibility Testing in Sputum Culture Negative Conversion

    Directory of Open Access Journals (Sweden)

    Takehiko Kobayashi

    2018-01-01

    Full Text Available Background: Among Mycobacterium abscessus complex infections, patients with M. abscessus subsp. abscessus (MAA lung disease are difficult to treat and no standard therapy has been established. Few reports have investigated the drug susceptibility of these strains. We retrospectively investigated how in vitro drug susceptibility testing (DST of MAA affects the induction of sputum conversion using pharmacotherapy. Methods: Patients with MAA lung disease diagnosed and treated between 2010 and 2014 at our hospital were enrolled and divided into Group A (sputum conversion without relapse within 1 year and Group B (persistent positive cultured or negative conversion with relapse. MAA was identified in M. abscessus using sequence with genotyping, and DST of MAA was performed. Results: We assessed 23 patients (9 males and 14 females. There were 8 patients in Group A and 15 in Group B. Higher prevalence of susceptible isolates for clarithromycin (CAM susceptibility on day 14 was noted in Group A than in Group B (P = 0.03 and no significant difference observed in the two groups for other drugs. Conclusions: In vitro DST of MAA, especially CAM susceptibility on day 14, affected the results of negative conversion. No other drugs were found to affect sputum culture negative conversion.

  2. Association between TYK2 polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis.

    Science.gov (United States)

    Lee, Y H; Bae, S-C

    2016-10-01

    This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802-0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706-0.889, p = 9.5 × 10(-7)), but not in Asians (OR = 1.127, 95% CI = 0.835-1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673-0.808, p rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661-0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. © The Author(s) 2016.

  3. The die is cast: arsenic exposure in early life and disease susceptibility.

    Science.gov (United States)

    Thomas, David J

    2013-12-16

    Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for the development and progression of disease in both species. Mode of action and dosimetric studies in the mouse may help assess the role of age at exposure as a factor in susceptibility to the toxic and carcinogenic effects of arsenic in humans.

  4. Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases

    OpenAIRE

    Oliveira,Marcio Sacramento de; Leon,Antônio Ponce de; Mattos,Inês Echenique; Koifman,Sérgio

    2011-01-01

    This study analyzed the association between air pollution and deaths from respiratory diseases, considering differential susceptibility according to gender. The authors used daily deaths from respiratory diseases (ICD-10, J00-J99), PM10, SO2, and O3 levels, and meteorological indicators in Volta Redonda, Rio de Janeiro State, Brazil, from January 2002 to December 2006. The association was estimated by Poisson regression using generalized additive models, where the increase in risk of deaths f...

  5. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  6. Spread of Ebola disease with susceptible exposed infected isolated recovered (SEIIhR) model

    Science.gov (United States)

    Azizah, Afina; Widyaningsih, Purnami; Retno Sari Saputro, Dewi

    2017-06-01

    Ebola is a deadly infectious disease and has caused an epidemic on several countries in West Africa. Mathematical modeling to study the spread of Ebola disease has been developed, including through models susceptible infected removed (SIR) and susceptible exposed infected removed (SEIR). Furthermore, susceptible exposed infected isolated recovered (SEIIhR) model has been derived. The aims of this research are to derive SEIIhR model for Ebola disease, to determine the patterns of its spread, to determine the equilibrium point and stability of the equilibrium point using phase plane analysis, and also to apply the SEIIhR model on Ebola epidemic in Sierra Leone in 2014. The SEIIhR model is a differential equation system. Pattern of ebola disease spread with SEIIhR model is solution of the differential equation system. The equilibrium point of SEIIhR model is unique and it is a disease-free equilibrium point that stable. Application of the model is based on the data Ebola epidemic in Sierra Leone. The free-disease equilibrium point (Se; Ee; Ie; Ihe; Re )=(5743865, 0, 0, 0, 0) is stable.

  7. Spread of Ebola disease with susceptible exposed infected isolated recovered (SEIIhR) model

    International Nuclear Information System (INIS)

    Azizah, Afina; Widyaningsih, Purnami; Saputro, Dewi Retno Sari

    2017-01-01

    Ebola is a deadly infectious disease and has caused an epidemic on several countries in West Africa. Mathematical modeling to study the spread of Ebola disease has been developed, including through models susceptible infected removed (SIR) and susceptible exposed infected removed (SEIR). Furthermore, susceptible exposed infected isolated recovered (SEII h R) model has been derived. The aims of this research are to derive SEII h R model for Ebola disease, to determine the patterns of its spread, to determine the equilibrium point and stability of the equilibrium point using phase plane analysis, and also to apply the SEII h R model on Ebola epidemic in Sierra Leone in 2014. The SEII h R model is a differential equation system. Pattern of ebola disease spread with SEII h R model is solution of the differential equation system. The equilibrium point of SEII h R model is unique and it is a disease-free equilibrium point that stable. Application of the model is based on the data Ebola epidemic in Sierra Leone. The free-disease equilibrium point ( S e ; E e ; I e ; I he ; R e )=(5743865, 0, 0, 0, 0) is stable. (paper)

  8. Cloning and expression analysis of innate immune genes from red sea bream to assess different susceptibility to megalocytivirus infection.

    Science.gov (United States)

    Jin, J W; Kim, Y C; Hong, S; Kim, M S; Jeong, J B; Jeong, H D

    2017-04-01

    As suggested by the Office International des Epizooties (OIE), fishes belonging to the genus Oplegnathus are more sensitive to megalocytivirus infection than other fish species including red sea bream (Pagrus major). To assess the roles of the innate immune response to these different susceptibilities, we cloned the genes encoding inflammatory factors including IL-8 and COX-2, and the antiviral factor like Mx from red sea bream for the first time and performed phylogenetic and structural analysis. Analysed expression levels of IL-1β, IL-8 and COX-2 and the antiviral factor like Mx genes performed with in vivo challenge experiment showed no difference in inflammatory gene expression or respiratory burst activity between red sea bream and rock bream (Oplegnathus fasciatus). However, the Mx gene expression levels in red sea bream were markedly higher than those in rock bream, suggesting the importance of type I interferon (IFN)-induced proteins, particularly Mx, during megalocytivirus infection, rather than inflammation-related genes. The in vitro challenge experiments using embryonic primary cultures derived from both fish species showed no difference in cytopathic effects (CPE), viral replication profiles, and inflammatory and Mx gene expression pattern between the two fish species. © 2016 John Wiley & Sons Ltd.

  9. In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

    Science.gov (United States)

    Copin, Richard; Vitry, Marie-Alice; Hanot Mambres, Delphine; Machelart, Arnaud; De Trez, Carl; Vanderwinden, Jean-Marie; Magez, Stefan; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean-Jacques; Muraille, Eric

    2012-01-01

    Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis. PMID:22479178

  10. Diversity of aging of the immune system classified in the cotton rat (Sigmodon hispidus) model of human infectious diseases.

    Science.gov (United States)

    Guichelaar, Teun; van Erp, Elisabeth A; Hoeboer, Jeroen; Smits, Noortje A M; van Els, Cécile A C M; Pieren, Daan K J; Luytjes, Willem

    2018-05-01

    Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed to define aging-related changes of the immune system of this species. Concomitantly, we asked whether the rate of immunological alterations may be stratified by physiological aberrations encountered during aging. With increasing age, cotton rats showed reduced frequencies of T cells, impaired induction of antibodies to RSV, higher incidence of aberrations of organs and signs of lipemia. Moreover, old animals expressed high biological heterogeneity, but the age-related reduction of T cell frequency was only observed in those specimens that displayed aberrant organs. Thus, cotton rats show age-related alterations of lymphocytes that can be classified by links with health status. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Studies on the susceptibility of ostriches (Struthio camelus to the Indonesian velogenic strain of Newcastle disease virus

    Directory of Open Access Journals (Sweden)

    Darminto

    1998-12-01

    Full Text Available Susceptibility of ostriches (Struthio camelus to the Indonesian velogenic strain of Newcastle disease virus (NDV was evaluated by artificial infection . Twelve - 5 to 6 week old ostriches were divided into 3 groups each containing 4 birds . The first group was inoculated through respiratory system by dropping directly the virus solution into the nostrils, while the second group was inoculated through digestive system by dropping directly the virus solution into the oesophagus, with the dose of infection 106ELDSo (50%-embryo lethal dose per bird . Meanwhile, the third group was treated as uninfected control . All infected birds developed antibody responses, but only two inoculated birds from the first group and two inoculated birds from the second group developed clinical signs of Newcastle disease (ND, with no specific pathological alterations . Infected birds, either sicks or healthy, excreted the challenge viruses through the respiratory system and still be detected up to the end of this experiment, ie . 15 days post-inoculation . The challenge viruses can be re-isolated from the brain, trachea, lungs, heart, liver, spleen, kidneys, small intestine, cecal-tonsil, and proventriculus of the infected birds . This study concludes that: (1 the ostriches are susceptible to the infection of the Indonesian velogenic strain ofNDV; (2 all infected birds developed immune responses, but only half of them develops el jtigi aj i disease ; (3 the infected birds excreted the challenge viruses for a considerable long time which may play role as the Mginiseti.ce ofinfectron the other healthy ostriches ; and (4 the challenge viruses can be re-isolated from various organs of the birds . .

  12. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

    DEFF Research Database (Denmark)

    Baillie, J. Kenneth; Bretherick, Andrew; Haley, Christopher S.

    2018-01-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcrip...

  13. Evolution, revolution and heresy in the genetics of infectious disease susceptibility

    Science.gov (United States)

    Hill, Adrian V. S.

    2012-01-01

    Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case–control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference. PMID:22312051

  14. Evolution, revolution and heresy in the genetics of infectious disease susceptibility.

    Science.gov (United States)

    Hill, Adrian V S

    2012-03-19

    Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case-control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference.

  15. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

    Science.gov (United States)

    Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

    2014-08-01

    Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to

  16. Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion.

    Science.gov (United States)

    Haley, Nicholas J; Rielinger, Rachel; Davenport, Kristen A; O'Rourke, Katherine; Mitchell, Gordon; Richt, Jürgen A

    2017-11-01

    In mammals, susceptibility to prion infection is primarily modulated by the host's cellular prion protein (PrP C ) sequence. In the sheep scrapie model, a graded scale of susceptibility has been established both in vivo and in vitro based on PrP C amino acids 136, 154 and 171, leading to global breeding programmes to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrP C allele conferring absolute resistance in cervids has been identified. To model the susceptibility of various naturally occurring and hypothetical cervid PrP C alleles in vitro, we compared the amplification rates and amyloid extension efficiencies of eight distinct CWD isolates in recombinant cervid PrP C substrates using real-time quaking-induced conversion. We hypothesized that the in vitro conversion characteristics of these isolates in cervid substrates would correlate to in vivo susceptibility - permitting susceptibility prediction for the rare alleles found in nature. We also predicted that hypothetical alleles with multiple resistance-associated codons would be more resistant to in vitro conversion than natural alleles with a single resistant codon. Our studies demonstrate that in vitro conversion metrics align with in vivo susceptibility, and that alleles with multiple amino acid substitutions, each influencing resistance independently, do not necessarily contribute additively to conversion resistance. Importantly, we found that the naturally occurring whitetail deer QGAK substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo is warranted.

  17. DMPD: Peptidoglycan signaling in innate immunity and inflammatory disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15802263 Peptidoglycan signaling in innate immunity and inflammatory disease. McDon...ald C, Inohara N, Nunez G. J Biol Chem. 2005 May 27;280(21):20177-80. Epub 2005 Mar 31. (.png) (.svg) (.html) (.csml) Show Peptidog...lycan signaling in innate immunity and inflammatory disease. PubmedID 15802263 Title Peptidog

  18. Challenges of Generating and Maintaining Protective Vaccine-Induced Immune Responses for Foot-and-Mouth Disease Virus in Pigs

    Science.gov (United States)

    Lyons, Nicholas A.; Lyoo, Young S.; King, Donald P.; Paton, David J.

    2016-01-01

    Vaccination can play a central role in the control of outbreaks of foot-and-mouth disease (FMD) by reducing both the impact of clinical disease and the extent of virus transmission between susceptible animals. Recent incursions of exotic FMD virus lineages into several East Asian countries have highlighted the difficulties of generating and maintaining an adequate immune response in vaccinated pigs. Factors that impact vaccine performance include (i) the potency, antigenic payload, and formulation of a vaccine; (ii) the antigenic match between the vaccine and the heterologous circulating field strain; and (iii) the regime (timing, frequency, and herd-level coverage) used to administer the vaccine. This review collates data from studies that have evaluated the performance of foot-and-mouth disease virus vaccines at the individual and population level in pigs and identifies research priorities that could provide new insights to improve vaccination in the future. PMID:27965966

  19. Differential expression of Toll-like receptor pathway genes in chicken embryo fibroblasts from chickens resistant and susceptible to Marek's disease.

    Science.gov (United States)

    Haunshi, Santosh; Cheng, Hans H

    2014-03-01

    The Toll-like receptor (TLR) signaling pathway is one of the innate immune defense mechanisms against pathogens in vertebrates and invertebrates. However, the role of TLR in non-MHC genetic resistance or susceptibility to Marek's disease (MD) in the chicken is yet to be elucidated. Chicken embryo fibroblast (CEF) cells from MD susceptible and resistant lines were infected either with Marek's disease virus (MDV) or treated with polyionosinic-polycytidylic acid, a synthetic analog of dsRNA, and the expression of TLR and pro-inflammatory cytokines was studied at 8 and 36 h posttreatment by quantitative reverse transcriptase PCR. Findings of the present study reveal that MDV infection and polyionosinic-polycytidylic acid treatment significantly elevated the mRNA expression of TLR3, IL6, and IL8 in both susceptible and resistant lines. Furthermore, basal expression levels in uninfected CEF for TLR3, TLR7, and IL8 genes were significantly higher in resistant chickens compared with those of susceptible chickens. Our results suggest that TLR3 together with pro-inflammatory cytokines may play a significant role in genetic resistance to MD.

  20. Immunopathology of immune reconstitution inflammatory syndrome in Whipple's disease.

    Science.gov (United States)

    Moos, Verena; Feurle, Gerhard E; Schinnerling, Katina; Geelhaar, Anika; Friebel, Julian; Allers, Kristina; Moter, Annette; Kikhney, Judith; Loddenkemper, Christoph; Kühl, Anja A; Erben, Ulrike; Fenollar, Florence; Raoult, Didier; Schneider, Thomas

    2013-03-01

    During antimicrobial treatment of classic Whipple's disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4(+) T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3(+), predominantly CD45RO(+)CD4(+) T cells. In the periphery, initial reduction of CD4(+) cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4(+) T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4(+) T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei-specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4(+) T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.

  1. ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF MICROBIAL PATHOGENS ISOLATED FROM CALVES WITH RESPIRATORY DISEASES

    OpenAIRE

    George Cosmin Nadas; Flore Chirila; Cosmina Bouari; Nicodim Fit

    2016-01-01

    Introduction: Respiratory disease in calves is an actual problem, a major cause of economic losses due to mortality, growth delay and improper development. These conditions are frequent in calves due to the weaning stress, transport and environmental changes. Aims: The aim of this study was the isolation of bacteria from 30 calves with respiratory disorders and their antibiotic susceptibility testing. Materials and methods: Samples were collected from calves with respiratory disorders...

  2. Genetic susceptibility to infectious disease: lessons from mouse models of leishmaniasis

    Czech Academy of Sciences Publication Activity Database

    Lipoldová, Marie; Demant, P.

    2006-01-01

    Roč. 7, č. 4 (2006), s. 294-305 ISSN 1471-0056 R&D Projects: GA ČR(CZ) GA310/03/1381 Grant - others:Howard Hughes Medical Institute(US) HHMI55000323 Institutional research plan: CEZ:AV0Z50520514 Keywords : leishmaniasis * susceptibility to infectious disease * modifying genes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 22.947, year: 2006

  3. THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

    OpenAIRE

    Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

    2011-01-01

    While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the orig...

  4. CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves' disease and modulates clinical phenotype of disease.

    Science.gov (United States)

    Pawlak-Adamska, Edyta; Frydecka, Irena; Bolanowski, Marek; Tomkiewicz, Anna; Jonkisz, Anna; Karabon, Lidia; Partyka, Anna; Nowak, Oskar; Szalinski, Marek; Daroszewski, Jacek

    2017-01-01

    Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR-RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)-PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT 16-21 )/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT 16-21 )GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT >21 )GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT >21 ]/[AT >21 ] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a

  5. Genetic susceptibility testing for chronic disease and intention for behavior change in healthy young adults.

    Science.gov (United States)

    Vassy, Jason L; Donelan, Karen; Hivert, Marie-France; Green, Robert C; Grant, Richard W

    2013-04-01

    Genetic testing for chronic disease susceptibility may motivate young adults for preventive behavior change. This nationally representative survey gave 521 young adults hypothetical scenarios of receiving genetic susceptibility results for heart disease, type 2 diabetes, and stroke and asked their (1) interest in such testing, (2) anticipated likelihood of improving diet and physical activity with high- and low-risk test results, and (3) readiness to make behavior change. Responses were analyzed by presence of established disease-risk factors. Respondents with high phenotypic diabetes risk reported increased likelihood of improving their diet and physical activity in response to high-risk results compared with those with low diabetes risk (odds ratio (OR), 1.82 (1.03, 3.21) for diet and OR, 2.64 (1.24, 5.64) for physical activity). In contrast, poor baseline diet (OR, 0.51 (0.27, 0.99)) and poor physical activity (OR, 0.53 (0.29, 0.99)) were associated with decreased likelihood of improving diet. Knowledge of genetic susceptibility may motivate young adults with higher personal diabetes risk for improvement in diet and exercise, but poor baseline behaviors are associated with decreased intention to make these changes. To be effective, genetic risk testing in young adults may need to be coupled with other strategies to enable behavior change.

  6. THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

    Science.gov (United States)

    Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

    2013-01-01

    While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the original features that molded cellular function were based upon mitochondrial-nuclear relationships established millions of years ago and were likely refined during prehistoric environmental selection events that today, are largely absent. Consequently, contemporary risk factors that influence our susceptibility to a variety of age-related diseases, including CVD were probably not part of the dynamics that defined the processes of mitochondrial – nuclear interaction, and thus, cell function. In this regard, the selective conditions that contributed to cellular functionality and evolution should be given more consideration when interpreting and designing experimental data and strategies. Finally, future studies that probe beyond epidemiologic associations are required. These studies will serve as the initial steps for addressing the provocative concept that contemporary human disease susceptibility is the result of selection events for mitochondrial function that increased chances for prehistoric human survival and reproductive success. PMID:21647091

  7. Th17 response and autophagy - main pathways implicated in the development of inflammatory bowel disease by genome-wide association studies: new factors involved in inflammatory bowel disease susceptibility

    Directory of Open Access Journals (Sweden)

    Roberto Díaz-Peña

    2015-09-01

    Full Text Available Inflammatory bowel disease (IBD is an entity that mainly includes ulcerative colitis (UC and Crohn's disease (CD. Improved health care, diet changes, and higher industrialization are associated with an increase in IBD prevalence. This supports the central role of environmental factors in the pathology of this disease. However, IBD also shows a relevant genetic component as shown by high heritability. Classic genetic studies showed relevant associations between IBD susceptibility and genes involved in the immune response. This is consistent with prior theories about IBD development. According to these, contact of the immune system with a high number of harmless antigens from the diet and the bacterial flora should originate tolerance while preserving response against pathogens. Failure to achieve this balance may originate the typical inflammatory response associated with IBD. Recently, genome-wide association studies (GWASs have confirmed the implication of the immune system, particularly the Th17 immune response, previously associated to other autoimmune diseases, and of autophagy. In this paper, the mechanisms involved in these two relevant pathways and their potential role in the pathogenesis of IBD are reviewed.

  8. Molecular and Bioenergetic Differences between Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Implications for Population Susceptibility to Diseases

    Science.gov (United States)

    Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Tarek, Mohamed; Cáceres del Carpio, Javier; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Vawter, Marquis P.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin

    2015-01-01

    The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP turnover rates and lower levels of ROS production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases. PMID:24200652

  9. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  10. Comparisons of protein profiles of beech bark disease resistant and susceptible American beech (Fagus grandifolia)

    Science.gov (United States)

    2013-01-01

    Background Beech bark disease is an insect-fungus complex that damages and often kills American beech trees and has major ecological and economic impacts on forests of the northeastern United States and southeastern Canadian forests. The disease begins when exotic beech scale insects feed on the bark of trees, and is followed by infection of damaged bark tissues by one of the Neonectria species of fungi. Proteomic analysis was conducted of beech bark proteins from diseased trees and healthy trees in areas heavily infested with beech bark disease. All of the diseased trees had signs of Neonectria infection such as cankers or fruiting bodies. In previous tests reported elsewhere, all of the diseased trees were demonstrated to be susceptible to the scale insect and all of the healthy trees were demonstrated to be resistant to the scale insect. Sixteen trees were sampled from eight geographically isolated stands, the sample consisting of 10 healthy (scale-resistant) and 6 diseased/infested (scale-susceptible) trees. Results Proteins were extracted from each tree and analysed in triplicate by isoelectric focusing followed by denaturing gel electrophoresis. Gels were stained and protein spots identified and intensity quantified, then a statistical model was fit to identify significant differences between trees. A subset of BBD differential proteins were analysed by mass spectrometry and matched to known protein sequences for identification. Identified proteins had homology to stress, insect, and pathogen related proteins in other plant systems. Protein spots significantly different in diseased and healthy trees having no stand or disease-by-stand interaction effects were identified. Conclusions Further study of these proteins should help to understand processes critical to resistance to beech bark disease and to develop biomarkers for use in tree breeding programs and for the selection of resistant trees prior to or in early stages of BBD development in stands. Early

  11. Survey of susceptibility to marbofloxacin in bacteria isolated from diseased pigs in Europe.

    Science.gov (United States)

    El Garch, F; Kroemer, S; Galland, D; Morrissey, I; Woehrle, F

    2017-06-17

    A monitoring programme of marbofloxacin susceptibility of bacteria from Europe causing respiratory tract infection and meningitis in pigs has been active since 1994 and 2002, respectively. Monitoring digestive, metritis and urinary tract infection (UTI) in pigs has been active since 2005 and susceptibility results until 2013 are presented. Minimum inhibitory concentration (MIC) was determined by broth microdilution. For MIC interpretation, Vétoquinol-evaluated breakpoints were applied. For digestive pathogens, Escherichia coli and Salmonella species (1717 and 300 isolates, respectively) exhibited 7.5 per cent resistance in E coli and no resistance in Salmonella species. Similarly, E coli from metritis (369 isolates) had 7.0 per cent resistance to marbofloxacin. However, E coli from UTI (633 isolates) had higher resistance (10.4 per cent). For Streptococcus suis causing meningitis (585 isolates), marbofloxacin susceptibility was very high with only 0.5 per cent resistance and 0.4 per cent resistance was observed with S suis causing respiratory disease (729 isolates). Other respiratory pathogens were also highly susceptible to marbofloxacin with no resistance in Actinobacillus pleuropneumoniae (647 isolates) or Bordetella bronchiseptica (504 isolates), 0.1 per cent resistance in Pasteurella multocida (1373 isolates) and 1.4 per cent resistance in Haemophilus parasuis (145 isolates). There was no apparent change in marbofloxacin MIC over time for any bacterial pathogen based on MIC 50/90 These data confirm previously published MIC results from porcine and other animal infections. British Veterinary Association.

  12. Role of the Innate Immune System in the Pathogenesis of Inflammatory Bowel Disease

    NARCIS (Netherlands)

    van Lierop, Pieter P. E.; Samsom, Janneke N.; Escher, Johanna C.; Nieuwenhuis, Edward E. S.

    Crohn disease and ulcerative colitis are chronic inflammatory diseases of the intestinal tract commonly denoted as inflammatory bowel diseases. It has been proposed that these diseases result from aberrant mucosal immune responses to nonpathogenic microbial residents of the intestines. Recently, it

  13. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    Science.gov (United States)

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.

    2009-01-01

    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  14. OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

    LENUS (Irish Health Repository)

    O'Brien, M

    2012-02-01

    BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

  15. Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.

    Directory of Open Access Journals (Sweden)

    Arne S Schaefer

    2009-02-01

    Full Text Available Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33-2.94; P = 6.9 x 10(-4 for generalized aggressive periodontitis, and 1.72 (1.06-2.76; P = 2.6 x 10(-2 for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases.

  16. Does Animal Behavior Underlie Covariation Between Hosts' Exposure to Infectious Agents and Susceptibility to Infection? Implications for Disease Dynamics

    NARCIS (Netherlands)

    Hawley, Dana M.; Etienne, Rampal S.; Ezenwa, Vanessa O.; Jolles, Anna E.

    2011-01-01

    Animal behavior is unique in influencing both components of the process of transmission of disease: exposure to infectious agents, and susceptibility to infection once exposed. To date, the influence of behavior on exposure versus susceptibility has largely been considered separately. Here, we ask

  17. Immune System and Its Link to Rheumatic Diseases

    Science.gov (United States)

    ... system, which contributes to the illness. So therapy targeting our own immune system can help alleviate the ... by the American College of Rheumatology Communications and Marketing Committee. This information is provided for general education ...

  18. Molecular signaling networks in regulation of immunity and disease

    DEFF Research Database (Denmark)

    Laursen, Janne Marie; Jensen, Stina Rikke; Sørensen, Morten

    and dynamic microbial communities with the immune cell compartment in the gut, and therefore the interaction between components from different gut bacteria can efficiently shape the phenotype of the immune response. A specialized antigenpresenting cell present at mucosal surfaces, the dendritic cell (DC......), plays a crucial role in shaping the nature of the adaptive/memorybased immune response after encountering inflammatory compounds. In the gut, the DC is continuously exposed to microbial and dietary components that are recognized by its innate pattern recognition receptors, and the phenotype developed...... in the DC during activation is of profound importance for the state of immune response and thereby also affects the inflammatory and metabolic status in tissues. We have shown that specific fermentation products from gut bacteria have distinct immunoregulatory effects that effectively inhibit...

  19. IRGM Variants and Susceptibility to Inflammatory Bowel Disease in the German Population

    Science.gov (United States)

    Bues, Stephanie; Stallhofer, Johannes; Fries, Christoph; Olszak, Torsten; Tsekeri, Eleni; Wetzke, Martin; Beigel, Florian; Steib, Christian; Friedrich, Matthias; Göke, Burkhard; Diegelmann, Julia; Czamara, Darina; Brand, Stephan

    2013-01-01

    Background & Aims Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study. Methodology/Principal Findings Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05–1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06–1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01–1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (passociations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05), which, however, did not remain significant after Bonferroni correction. Conclusions/Significance Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD. PMID:23365659

  20. Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

    Science.gov (United States)

    Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

    2017-02-01

    Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Research advances in susceptibility genes and their role in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    XUAN Shiying

    2016-03-01

    Full Text Available Currently the incidence of nonalcoholic fatty liver disease (NAFLD is increasing, and the age of onset is getting younger worldwide, resulting in a heavy economic burden for both individuals and the society. Since NAFLD is closely related to heredity, metabolism, and the environment, genetic factors play an important role in the development and progression of NAFLD. With the development and wide application of the techniques from the genome-wide association studies, new research advances have been achieved in the susceptibility genes of NAFLD. This review summarizes the related research findings at home and abroad, and investigates the pathogenic factors for NAFLD and related mechanisms with a focus on the polymorphisms of susceptibility genes.

  2. The Neuromodulation of the Intestinal Immune System and Its Relevance in Inflammatory Bowel Disease.

    Science.gov (United States)

    Di Giovangiulio, Martina; Verheijden, Simon; Bosmans, Goele; Stakenborg, Nathalie; Boeckxstaens, Guy E; Matteoli, Gianluca

    2015-01-01

    One of the main tasks of the immune system is to discriminate and appropriately react to "danger" or "non-danger" signals. This is crucial in the gastrointestinal tract, where the immune system is confronted with a myriad of food antigens and symbiotic microflora that are in constant contact with the mucosa, in addition to any potential pathogens. This large number of antigens and commensal microflora, which are essential for providing vital nutrients, must be tolerated by the intestinal immune system to prevent aberrant inflammation. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homeostasis and to prevent immune activation indiscriminately against all luminal antigens. Loss of this delicate equilibrium can lead to chronic activation of the intestinal immune response resulting in intestinal disorders, such as inflammatory bowel diseases (IBD). In order to maintain homeostasis, the immune system has evolved diverse regulatory strategies including additional non-immunological actors able to control the immune response. Accumulating evidence strongly indicates a bidirectional link between the two systems in which the brain modulates the immune response via the detection of circulating cytokines and via direct afferent input from sensory fibers and from enteric neurons. In the current review, we will highlight the most recent findings regarding the cross-talk between the nervous system and the mucosal immune system and will discuss the potential use of these neuronal circuits and neuromediators as novel therapeutic tools to reestablish immune tolerance and treat intestinal chronic inflammation.

  3. Senescence of the adaptive immune system in health and aging-associated autoimmune disease

    NARCIS (Netherlands)

    van der Geest, Kornelis Stephan Mario

    2015-01-01

    Aging of the immune system may contribute to the development of aging-associated autoimmune diseases, such as giant cell arteritis, polymyalgia rheumatica and rheumatoid arthritis. The aim of this thesis was to identify aging-dependent changes of the adaptive immune system that promote autoimmunity

  4. A short history of research on immunity to infectious diseases in fish

    NARCIS (Netherlands)

    Muiswinkel, van W.B.; Nakao, M.

    2014-01-01

    This review describes the history of research on immunity to infectious diseases of fish in the period between 1965 and today. Special attention is paid to those studies, which are dealing with the interaction between immune system and invading pathogens in bony fish. Moreover, additional biographic

  5. Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease

    Science.gov (United States)

    2012-01-01

    Introduction The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans. Methods RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts. Results After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001. Conclusions The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in

  6. AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.

    Science.gov (United States)

    Antonelli, Ray; Shao, Kan; Thomas, David J; Sams, Reeder; Cowden, John

    2014-07-01

    Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.

  7. The use of simple indicators for detecting potential coronary heart disease susceptibility in the air traffic controller population.

    Science.gov (United States)

    1972-05-01

    An analysis was made of an eight-year interval change in several indicators of coronary heart disease (CHD) susceptibility as measured on 475 male air traffic control (ATC) personnel. The initial measurements were obtained from these personnel as ATC...

  8. The use of simple indicators for detecting potential coronary heart disease susceptibility in the third-class airman population.

    Science.gov (United States)

    1972-07-01

    An analysis was made of an eight-year interval change in several Framingham Heart Study (FHS) indicators of coronary heart disease (CHD) susceptibility as measured on 475 male air traffic control (ATC) personnel. The initial measurements were obtaine...

  9. Executive Summary: Variation in Susceptibility to Ozone-Induced Health Effects in Rodent Models of Cardiometabolic Disease

    Science.gov (United States)

    Seven million premature deaths occur annually due to air pollution worldwide, of which ~80% are attributed to exacerbation of cardiovascular disease (CVD}, necessitating greater attention to understanding the causes of susceptibility to air pollution in this sector of population....

  10. Beyond disease susceptibility-Leveraging genome-wide association studies for new insights into complex disease biology.

    Science.gov (United States)

    Lee, J C

    2017-12-01

    Genetic studies in complex diseases have been highly successful, but have also been largely one-dimensional: predominantly focusing on the genetic contribution to disease susceptibility. While this is undoubtedly important-indeed it is a pre-requisite for understanding the mechanisms underlying disease development-there are many other important aspects of disease biology that have received comparatively little attention. In this review, I will discuss how existing genetic data can be leveraged to provide new insights into other aspects of disease biology, why such insights could change the way we think about complex disease, and how this could provide opportunities for better therapies and/or facilitate personalised medicine. To do this, I will use the example of Crohn's disease-a chronic form of inflammatory bowel disease that has been one of the main success stories in complex disease genetics. Indeed, thanks to genetic studies, we now have a much more detailed understanding of the processes involved in Crohn's disease development, but still know relatively little about what determines the subsequent disease course (prognosis) and why this differs so considerably between individuals. I will discuss how we came to realise that genetic variation plays an important role in determining disease prognosis and how this has changed the way we think about Crohn's disease genetics. This will illustrate how phenotypic data can be used to leverage new insights from genetic data and will provide a broadly applicable framework that could yield new insights into the biology of multiple diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. How useful is a history of rubella vaccination for determination of disease susceptibility? A cross-sectional study at a public funded health clinic in Malaysia

    Directory of Open Access Journals (Sweden)

    Cheong Ai Theng

    2013-01-01

    Full Text Available Abstract Background Identification of pregnant women susceptible to rubella is important as vaccination can be given postpartum to prevent future risks of congenital rubella syndrome. However, in Malaysia, rubella antibody screening is not offered routinely to pregnant women in public funded health clinics due to cost constraint. Instead, a history of rubella vaccination is asked to be provided to establish the women’s risk for rubella infection. The usefulness of this history, however, is not established. Thus, this paper aimed to determine the usefulness of a history of rubella vaccination in determining rubella susceptibility in pregnant women. Methods A cross-sectional study was conducted on 500 pregnant women attending a public funded health clinic. Face-to-face interviews were conducted, and demographic data and history of rubella vaccination were obtained. Anti-rubella IgG test was performed. Results A majority of the women (66.6% had a positive vaccination history. Of these, 92.2% women were immune. A third (33.4% of the women had a negative or unknown vaccination history, but 81.4% of them were immune to rubella. The sensitivity and specificity of a history of rubella vaccination in identifying disease susceptibility was 54.4% (95% CI: 40.7, 67.4% and 69.3% (95% CI: 64.7, 73.5% respectively; the positive predictive value was 18.6% (95% CI: 13.1, 25.5% and the negative predictive value was 92.2% (95% CI: 88.6, 94.7%. Conclusions A vaccination history of rubella had a poor diagnostic value in predicting rubella susceptibility. However, obtaining a vaccination history is inexpensive compared with performing a serological test. A cost-utility analysis would be useful in determining which test (history versus serological test is more cost-effective in a country with resource constraint.

  12. How useful is a history of rubella vaccination for determination of disease susceptibility? A cross-sectional study at a public funded health clinic in Malaysia.

    Science.gov (United States)

    Cheong, Ai Theng; Tong, Seng Fah; Khoo, Ee Ming

    2013-01-31

    Identification of pregnant women susceptible to rubella is important as vaccination can be given postpartum to prevent future risks of congenital rubella syndrome. However, in Malaysia, rubella antibody screening is not offered routinely to pregnant women in public funded health clinics due to cost constraint. Instead, a history of rubella vaccination is asked to be provided to establish the women's risk for rubella infection. The usefulness of this history, however, is not established. Thus, this paper aimed to determine the usefulness of a history of rubella vaccination in determining rubella susceptibility in pregnant women. A cross-sectional study was conducted on 500 pregnant women attending a public funded health clinic. Face-to-face interviews were conducted, and demographic data and history of rubella vaccination were obtained. Anti-rubella IgG test was performed. A majority of the women (66.6%) had a positive vaccination history. Of these, 92.2% women were immune. A third (33.4%) of the women had a negative or unknown vaccination history, but 81.4% of them were immune to rubella. The sensitivity and specificity of a history of rubella vaccination in identifying disease susceptibility was 54.4% (95% CI: 40.7, 67.4%) and 69.3% (95% CI: 64.7, 73.5%) respectively; the positive predictive value was 18.6% (95% CI: 13.1, 25.5%) and the negative predictive value was 92.2% (95% CI: 88.6, 94.7%). A vaccination history of rubella had a poor diagnostic value in predicting rubella susceptibility. However, obtaining a vaccination history is inexpensive compared with performing a serological test. A cost-utility analysis would be useful in determining which test (history versus serological test) is more cost-effective in a country with resource constraint.

  13. The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases

    Science.gov (United States)

    Liu, Meifang; Zhang, Cai

    2017-01-01

    Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases. Here, we review the relationships between the ILC subsets and their functions in immune-mediated liver diseases, and discuss their therapeutic potential based on current knowledge about the functional roles of these cells in liver diseases. PMID:28659927

  14. Peroxisome Proliferator-Activated Receptor Genetic Polymorphisms and Nonalcoholic Fatty Liver Disease: Any Role in Disease Susceptibility?

    Directory of Open Access Journals (Sweden)

    Paola Dongiovanni

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD defines a wide spectrum of liver diseases that extend from simple steatosis, that is, increased hepatic lipid content, to nonalcoholic steatohepatitis (NASH, a condition that may progress to cirrhosis with its associated complications. Nuclear hormone receptors act as intracellular lipid sensors that coordinate genetic networks regulating lipid metabolism and energy utilization. This family of transcription factors, in particular peroxisome proliferator-activated receptors (PPARs, represents attractive drug targets for the management of NAFLD and NASH, as well as related conditions such as type 2 diabetes and the metabolic syndrome. The impact on the regulation of lipid metabolism observed for PPARs has led to the hypothesis that genetic variants within the human PPARs genes may be associated with human disease such as NAFLD, the metabolic syndrome, and/or coronary heart disease. Here we review the available evidence on the association between PPARs genetic polymorphism and the susceptibility to NAFLD and NASH, and we provide a meta-analysis of the available evidence. The impact of PPAR variants on the susceptibility to NASH in specific subgroup of patients, and in particular on the response to therapies, especially those targeting PPARs, represents promising new areas of investigation.

  15. Boosting innate immunity to sustainably control diseases in crops.

    Science.gov (United States)

    Nicaise, Valerie

    2017-10-01

    Viruses cause epidemics in all major crops, threatening global food security. The development of efficient and durable resistance able to withstand viral attacks represents a major challenge for agronomy, and relies greatly on the understanding of the molecular dialogue between viral pathogens and their hosts. Research over the last decades provided substantial advances in the field of plant-virus interactions. Remarkably, the advent of studies of plant innate immunity has recently offered new strategies exploitable in the field. This review summarizes the recent breakthroughs that define the mechanisms underlying antiviral innate immunity in plants, and emphasizes the importance of integrating that knowledge into crop improvement actions, particularly by exploiting the insights related to immune receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. NFKBIZ polymorphisms and susceptibility to pneumococcal disease in European and African populations

    Science.gov (United States)

    Chapman, Stephen J; Khor, Chiea C; Vannberg, Fredrik O; Rautanen, Anna; Segal, Shelley; Moore, Catrin E; Davies, Robert J O; Day, Nicholas P; Peshu, Norbert; Crook, Derrick W; Berkley, James A; Williams, Thomas N; Scott, J Anthony; Hill, Adrian V S

    2011-01-01

    The proinflammatory transcription factor nuclear factor-kappaB (NF-κB) plays a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-κB inhibitor IκB-α associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IκB-ζ gene NFKBIZ in the development of invasive pneumococcal disease has not previously been reported. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n=1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium block and all four polymorphisms within the equivalent, shorter Kenyan linkage disequilibrium block displayed either significant association with invasive pneumococcal disease or a trend towards association. For each polymorphism, heterozygosity was associated with protection from invasive pneumococcal disease when compared to the combined homozygous states (e.g. for rs600718, Mantel-Haenszel 2×2 χ2=7.576, P=0.006, OR=0.67, 95% CI for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2×2 χ2=8.715, P=0.003, OR=0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to invasive pneumococcal disease in humans. The study of multiple populations may aid fine-mapping of associations within extensive regions of strong linkage disequilibrium (‘transethnic mapping’). PMID:19798075

  17. Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease

    Directory of Open Access Journals (Sweden)

    Margoth Moreno

    2010-11-01

    Full Text Available Therapeutic failure of benznidazole (BZ is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC50 to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC50 of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out.

  18. Role of sex hormones and the vaginal microbiome in susceptibility and mucosal immunity to HIV-1 in the female genital tract.

    Science.gov (United States)

    Vitali, Danielle; Wessels, Jocelyn M; Kaushic, Charu

    2017-09-12

    While the prevalence of Human immunodeficiency virus-1 (HIV-1) infection has stabilized globally, it continues to be the leading cause of death among women of reproductive age. The majority of new infections are transmitted heterosexually, and women have consistently been found to be more susceptible to HIV-1 infection during heterosexual intercourse compared to men. This emphasizes the need for a deeper understanding of how the microenvironment in the female genital tract (FGT) could influence HIV-1 acquisition. This short review focuses on our current understanding of the interplay between estrogen, progesterone, and the cervicovaginal microbiome and their immunomodulatory effects on the FGT. The role of hormonal contraceptives and bacterial vaginosis on tissue inflammation, T cell immunity and HIV-1 susceptibility is discussed. Taken together, this review provides valuable information for the future development of multi-purpose interventions to prevent HIV-1 infection in women.

  19. Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis.

    Science.gov (United States)

    Wang, Yun; Liu, Shengyuan; Wang, Jingjing; Zhang, Jie; Hua, Yaqiong; Li, Hua; Tan, Huibiao; Kuai, Bin; Wang, Biao; Sheng, Sitong

    2017-08-16

    Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer's disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case-control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817-1.037, P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635-0.974, P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647-0.990, P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748-0.985, P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763-0.994, P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

  20. Cooler temperatures destabilize RNA interference and increase susceptibility of disease vector mosquitoes to viral infection.

    Directory of Open Access Journals (Sweden)

    Zach N Adelman

    Full Text Available The impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus, exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference (RNAi pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery.We utilized transgenic "sensor" strains of Aedes aegypti to examine the role of temperature on RNA silencing. These "sensor" strains express EGFP only when RNAi is inhibited; for example, after knockdown of the effector proteins Dicer-2 (DCR-2 or Argonaute-2 (AGO-2. We observed an increase in EGFP expression in transgenic sensor mosquitoes reared at 18°C as compared with 28°C. Changes in expression were dependent on the presence of an inverted repeat with homology to a portion of the EGFP sequence, as transgenic strains lacking this sequence, the double stranded RNA (dsRNA trigger for RNAi, showed no change in EGFP expression when reared at 18°C. Sequencing small RNAs in sensor mosquitoes reared at low temperature revealed normal processing of dsRNA substrates, suggesting the observed deficiency in RNAi occurs downstream of DCR-2. Rearing at cooler temperatures also predisposed mosquitoes to higher levels of infection with both chikungunya and yellow fever viruses.This data suggest that microclimates, such as those present in mosquito breeding sites, as well as more general climactic variables may influence the dynamics of mosquito-borne viral diseases by affecting the antiviral immunity of disease vectors.

  1. Protein-Energy Malnutrition (PEM is Believed to Lead to an Increased Susceptibility to Infection, or cause Impaired Immunity

    Directory of Open Access Journals (Sweden)

    Mellova Amir Masrizal

    2003-08-01

    Full Text Available Infection, occurring with malnutrition, is a major cause of morbidity in all age groups and is responsible for two-thirds of all death under 5 yr of age in developing countries. Many cells of the immune system are known to depend for their function on metabolic pathways that employ various nutrients as critical factors. The most consistent changes in immune competence in PEM are in cell-mediated immunity, the bactericidal function of neutrophils, the complement system, the secretory immunoglobin A, and antibody response.

  2. Transcriptional profiles of pulmonary innate immune responses to isogenic antibiotic-susceptible and multidrug-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Tam, Vincent H; Pérez, Cynthia; Ledesma, Kimberly R; Lewis, Russell E

    2018-04-01

    The virulence of an isogenic pair of Pseudomonas aeruginosa strains was studied under similar experimental conditions in two animal infection models. The time to death was significantly longer for the multidrug resistant (MDR) than the wild-type strain. The transcriptional profiles of 84 innate immune response genes in the lungs of immune competent Balb/C mice were further compared. Significantly weaker expression of genes involved in production of soluble pattern recognition receptor and complement were observed in animals infected with the MDR strain. Altered patterns of innate immune system activation may explain the attenuated virulence in MDR bacteria. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

  3. Leptin, immune responses and autoimmune disease. Perspectives on the use of leptin antagonists.

    Science.gov (United States)

    Peelman, F; Iserentant, H; Eyckerman, S; Zabeau, L; Tavernier, J

    2005-01-01

    The pivotal role of leptin in regulating body weight and energy homeostasis is very well established. More recently, leptin also emerged as an important regulator of T-cell-dependent immunity. Reduced leptin levels, as observed during periods of starvation, correlate with an impaired cellular immune response, whereby especially the T(H)1 pro-inflammatory immune response appears to be affected. Physiologically, this could reflect the high energy demand of such processes, which are suppressed in animals or people with nutrient shortage. Several autoimmune diseases are T(H)1 T-cell dependent. In line with a pro-inflammatory role for leptin, animal models of leptin deficiency are markedly resistant to a variety of T-cell dependent autoimmune diseases. Here, we review the role of leptin in immune responses, with emphasis on autoimmune diseases. The design and potential use of leptin antagonists is also discussed.

  4. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2013-01-01

    Full Text Available Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (multiple sclerosis, and autism (, but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD to 33% (MS of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as to the disease itself.

  5. Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans.

    Science.gov (United States)

    Yang, Suk-Kyun; Hong, Myunghee; Choi, Hyunchul; Zhao, Wanting; Jung, Yusun; Haritunians, Talin; Ye, Byong Duk; Kim, Kyung-Jo; Park, Sang Hyoung; Lee, Inchul; Kim, Won Ho; Cheon, Jae Hee; Kim, Young-Ho; Jang, Byung Ik; Kim, Hyun-Soo; Choi, Jai Hyun; Koo, Ja Seol; Lee, Ji Hyun; Jung, Sung-Ae; Shin, Hyoung Doo; Kang, Daehee; Youn, Hee-Shang; Taylor, Kent D; Rotter, Jerome I; Liu, Jianjun; McGovern, Dermot P B; Song, Kyuyoung

    2015-01-01

    Crohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population. Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls. We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans. Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.

  6. [Validation of the modified algorithm for predicting host susceptibility to viruses taking into account susceptibility parameters of primary target cell cultures and natural immunity factors].

    Science.gov (United States)

    Zhukov, V A; Shishkina, L N; Safatov, A S; Sergeev, A A; P'iankov, O V; Petrishchenko, V A; Zaĭtsev, B N; Toporkov, V S; Sergeev, A N; Nesvizhskiĭ, Iu V; Vorob'ev, A A

    2010-01-01

    The paper presents results of testing a modified algorithm for predicting virus ID50 values in a host of interest by extrapolation from a model host taking into account immune neutralizing factors and thermal inactivation of the virus. The method was tested for A/Aichi/2/68 influenza virus in SPF Wistar rats, SPF CD-1 mice and conventional ICR mice. Each species was used as a host of interest while the other two served as model hosts. Primary lung and trachea cells and secretory factors of the rats' airway epithelium were used to measure parameters needed for the purpose of prediction. Predicted ID50 values were not significantly different (p = 0.05) from those experimentally measured in vivo. The study was supported by ISTC/DARPA Agreement 450p.

  7. Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

    National Research Council Canada - National Science Library

    Bovbjerg, Dana

    2003-01-01

    The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against caner...

  8. Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

    National Research Council Canada - National Science Library

    Bovbjerg, Dana

    2001-01-01

    The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

  9. Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

    National Research Council Canada - National Science Library

    Bovbjerg, Dana

    2002-01-01

    The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

  10. Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

    National Research Council Canada - National Science Library

    Bovbjerg, Dana

    2000-01-01

    The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

  11. Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

    National Research Council Canada - National Science Library

    Bovbjerg, Dana

    1999-01-01

    The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

  12. MAVS is not a Likely Susceptibility Locus for Addison's Disease and Type 1 Diabetes.

    Science.gov (United States)

    Zurawek, Magdalena; Fichna, Marta; Kazimierska, Marta; Fichna, Piotr; Dzikiewicz-Krawczyk, Agnieszka; Przybylski, Grzegorz; Ruchala, Marek; Nowak, Jerzy

    2017-06-01

    Mitochondrial antiviral signaling (MAVS) protein is an intracellular adaptor molecule, downstream of viral sensors, retinoid acid-inducible gene I (RIG-I)-like receptors (RLRs). Impaired antiviral cell signaling might contribute to autoimmunity. Studies have recently shown variations in genes encoding RLRs as risk factors for autoimmune diseases. We investigated whether MAVS coding polymorphisms are associated with Addison's disease (AD) and type 1 diabetes (T1D) in Polish population. We genotyped 140 AD, 532 T1D patients and 600 healthy controls for MAVS rs17857295, rs7262903, rs45437096 and rs7269320. Genotyping was performed by TaqMan assays. Distribution of the MAVS genotypes and alleles did not reveal significant differences between patients and controls (p > 0.05). This analysis did not indicate the association of the MAVS locus with susceptibility to AD and T1D.

  13. IL-35, a hallmark of immune-regulation in cancer progression, chronic infections and inflammatory diseases.

    Science.gov (United States)

    Teymouri, Manouchehr; Pirro, Matteo; Fallarino, Francesca; Gargaro, Marco; Sahebkar, Amirhosein

    2018-03-25

    Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target. © 2018 UICC.

  14. Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Fuu-Jen Tsai

    Full Text Available Kawasaki disease (KD is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit gene: rs1873668 (p = 9.52×10⁻⁵, rs4243399 (p = 9.93×10⁻⁵, and rs16849083 (p = 9.93×10⁻⁵. We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1 gene (rs149481, p(best = 4.61×10⁻⁵. Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667 clustered in an area containing immunoglobulin heavy chain variable regions genes, with p(best-values between 2.08×10⁻⁵ and 8.93×10⁻⁶, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD.

  15. Roles and Regulation of Gastrointestinal Eosinophils in Immunity and Disease

    Science.gov (United States)

    Jung, YunJae; Rothenberg, Marc E.

    2014-01-01

    Eosinophils have been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergy reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system. PMID:25049430

  16. Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility.

    Science.gov (United States)

    Birse, Kenzie; Arnold, Kelly B; Novak, Richard M; McCorrister, Stuart; Shaw, Souradet; Westmacott, Garrett R; Ball, Terry B; Lauffenburger, Douglas A; Burgener, Adam

    2015-09-01

    The variable infectivity and transmissibility of HIV/SHIV has been recently associated with the menstrual cycle, with particular susceptibility observed during the luteal phase in nonhuman primate models and ex vivo human explant cultures, but the mechanism is poorly understood. Here, we performed an unbiased, mass spectrometry-based proteomic analysis to better understand the mucosal immunological processes underpinning this observed susceptibility to HIV infection. Cervicovaginal lavage samples (n = 19) were collected, characterized as follicular or luteal phase using days since last menstrual period, and analyzed by tandem mass spectrometry. Biological insights from these data were gained using a spectrum of computational methods, including hierarchical clustering, pathway analysis, gene set enrichment analysis, and partial least-squares discriminant analysis with LASSO feature selection. Of the 384 proteins identified, 43 were differentially abundant between phases (P HIV. Recent studies have discovered an enhanced susceptibility to HIV infection during the progesterone-dominant luteal phase of the menstrual cycle. However, the mechanism responsible for this enhanced susceptibility has not yet been determined. Understanding the source of this vulnerability will be important for designing efficacious HIV prevention technologies for women. Furthermore, these findings may also be extrapolated to better understand the impact of exogenous hormone application, such as the use of hormonal contraceptives, on HIV acquisition risk. Hormonal contraceptives are the most widely used contraceptive method in sub-Saharan Africa, the most HIV-burdened area of the world. For this reason, research conducted to better understand how hormones impact host immunity and susceptibility factors important for HIV infection is a global health priority. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. How glyphosate affects plant disease development: it is more than enhanced susceptibility.

    Science.gov (United States)

    Hammerschmidt, Ray

    2018-05-01

    Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

    Science.gov (United States)

    Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

    2017-08-01

    MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

  19. Immunizations

    Science.gov (United States)

    ... vaccine leaves a person unprotected and still at risk for getting a disease. Other vaccinations require a booster shot every few years to ... who get diseases like mumps may be at risk for side effects of the illness, such ... children). Vaccinations are about protecting you in the future, not ...

  20. A short history of research on immunity to infectious diseases in fish.

    Science.gov (United States)

    Van Muiswinkel, Willem B; Nakao, Miki

    2014-04-01

    This review describes the history of research on immunity to infectious diseases of fish in the period between 1965 and today. Special attention is paid to those studies, which are dealing with the interaction between immune system and invading pathogens in bony fish. Moreover, additional biographic information will be provided of people involved. In the 1960s and 1970s the focus of most studies was on humoral (Ig, B-cell) responses. Thorough studies on specific cellular (T-cell) responses and innate immunity (lectins, lysozyme, interferon, phagocytic cells) became available later. In the period between 1980 and today an overwhelming amount of data on regulation (e.g. cell cooperation, cytokines) and cell surface receptors (e.g. T-cell receptor; MHC) was published. It became also clear, that innate responses were often interacting with the acquired immune responses. Fish turned out to be vertebrates like all others with a sophisticated immune system showing specificity and memory. These basic data on the immune system could be applied in vaccination or in selection of disease resistant fish. Successful vaccines against bacterial diseases became available in the 1970s and 1980s. Effective anti-viral vaccines appeared from the 1980s onwards. There is no doubt, that Fish Immunology has become a flourishing science by the end of the 20th century and has contributed to our understanding of fish diseases as well as the success of aquaculture. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Crohn’s disease: Mucosal immunology and immune modulating therapy

    NARCIS (Netherlands)

    Peters, C.P.

    2014-01-01

    Crohn’s disease (CD) and ulcerative colitis (UC) are debilitating chronic diseases that affect millions of people worldwide, profoundly impacting patient quality of life and incurring large costs in terms of treatment and lost productivity. While current interventions ameliorate disease symptoms,

  2. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

    Science.gov (United States)

    Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nöthen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cécile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Céline; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sánchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Longstreth, W T; Fairchild, Thomas J; Bossù, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairén, Mònica Díez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleó, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Muñoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stählbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, María J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-François; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D

    2017-09-01

    We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

  3. Rearing environment affects development of the immune system in neonates

    NARCIS (Netherlands)

    Inman, C.F.; Haverson, K.; Konstantinov, S.R.; Jones, P.H.; Harris, C.; Smidt, H.; Miller, B.; Bailey, M.; Stokes, C.

    2010-01-01

    P>Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect

  4. Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK in disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Chia-Jung Chang

    Full Text Available The BLK and CD40 loci have been associated with Kawasaki disease (KD in two genome-wide association studies (GWAS conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31. We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC population and the expression of BLK in the peripheral blood leukocytes (leukocytes of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

  5. Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada

    Directory of Open Access Journals (Sweden)

    R. Michele Anholt

    2017-12-01

    Full Text Available Bovine respiratory disease (BRD is the most important illness of feedlot cattle. Disease management targets the associated bacterial pathogens, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni, and Trueperella pyogenes. We conducted a cross-sectional study to measure the frequencies of antimicrobial-resistant BRD pathogens using a collaborative network of veterinarians, industry, government, and a diagnostic laboratory. Seven private veterinary practices in southern Alberta collected samples from both living and dead BRD-affected animals at commercial feedlots. Susceptibility testing of 745 isolates showed that 100% of the M. haemolytica, M. bovis, P. multocida, and T. pyogenes isolates and 66.7% of the H. somni isolates were resistant to at least one antimicrobial class. Resistance to macrolide antimicrobials (90.2% of all isolates was notable for their importance to beef production and human medicine. Multidrug resistance (MDR was high in all target pathogens with 47.2% of the isolates resistant to four or five antimicrobial classes and 24.0% resistance to six to nine classes. We compared the MDR profiles of isolates from two feedlots serviced by different veterinary practices. Differences in the average number of resistant classes were found for M. haemolytica (p < 0.001 and P. multocida (p = 0.002. Compared to previous studies, this study suggests an increasing trend of resistance in BRD pathogens against the antimicrobials used to manage the disease in Alberta. For the veterinary clinician, the results emphasize the importance of ongoing susceptibility testing of BRD pathogens to inform treatment protocols. Surveillance studies that collect additional epidemiological information and manage sampling bias will be necessary to develop strategies to limit the spread of resistance.

  6. ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF MICROBIAL PATHOGENS ISOLATED FROM CALVES WITH RESPIRATORY DISEASES

    Directory of Open Access Journals (Sweden)

    George Cosmin Nadas

    2016-11-01

    Full Text Available Introduction: Respiratory disease in calves is an actual problem, a major cause of economic losses due to mortality, growth delay and improper development. These conditions are frequent in calves due to the weaning stress, transport and environmental changes. Aims: The aim of this study was the isolation of bacteria from 30 calves with respiratory disorders and their antibiotic susceptibility testing. Materials and methods: Samples were collected from calves with respiratory disorders (nasal discharge aged 6 to 9 weeks in 2 series, using sterile swabs. Samples were initially inoculated on blood agar and MacConkey agar following the characteristics of the colonies and microscopic examination that enabled the identification of bacterial species. Isolated strains were used to flood Mueller-Hinton agar to carry out sensitivity testing. The antibiotics tested were represented by: Amoxicillin with clavulanic acid, Gentamicin, Florfenicol, Enrofloxacin, Marbofloxacin, Penicillin G, Cefquinone, Tulathromycin, Ceftiofur, Tylosin and Cephalotin. Results: Genus Streptococcus have been identified in 23 samples, followed by Staphylococcus identified in 14 samples, and Bacillus spp., in 10 nasal swabs; The most common bacteria associations were represented by Streptococcus-Staphylococcus, Streptococcus-Staphylococcus-Bacillus, and Streptococcus-E.coli. The most efficient antibiotic was Cefquinome (Cobactan, followed by Penicillin G and Amoxicillin with clavulanic acid (Amoxiclav; the least effective antibiotics were Florfenicol and Tulathromycin. Conclusions: The study carried out on nasal discharge samples collected from calves with respiratory disorders and their antimicrobial profile testing led to the following conclusions: 1 Low susceptibility to Florfenicol is caused by previous treatments when this molecule was excessively used and without prior sensitivity testing. 2 Cefquinome may represent an emergency therapeutic antibiotic for respiratory

  7. Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility.

    Science.gov (United States)

    Lin, Hsiu-Ling; Ueng, Kwo-Chang; Hsieh, Yih-Shou; Chiang, Whei-Ling; Yang, Shun-Fa; Chu, Shu-Chen

    2012-09-01

    Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.

  8. Urbanized South Asians' susceptibility to coronary heart disease: The high-heat food preparation hypothesis.

    Science.gov (United States)

    Kakde, Smitha; Bhopal, Raj S; Bhardwaj, Swati; Misra, Anoop

    2017-01-01

    Known risk factors do not fully explain the comparatively high susceptibility to coronary heart disease (CHD) in South Asians (Indian, Pakistani, Bangladeshi, and Sri Lankan populations in South Asia and overseas). The search for explanatory hypotheses and cofactors that raise susceptibility of South Asians to CHD continues. The aim of this study was to propose "the high-heat food preparation hypothesis," where neo-formed contaminants (NFCs) such as trans-fatty acids (TFAs) and advanced glycation end-products (AGEs) are the cofactors. We reviewed the actions of AGEs and TFAs, the burden of these products in tissues and blood in South Asians, the relationship between these products and CHD, the effects of preparing food and reheating oils at high temperatures on NFCs, and the foods and mode of preparation in South Asian and Chinese cuisines. Animal and human studies show NFCs increase the risk for CHD. Evidence on the consumption and body burden of these products across ethnic groups is not available, and comparable data on the NFC content of the cuisine of South Asians and potential comparison populations (e.g., the Chinese with lower CHD rates) are limited. South Asians' cuisine is dominated by frying and roasting techniques that use high temperatures. South Asian foods have high TFA content primarily through the use of partially hydrogenated fats, reheated oils, and high-heat cooking. Reheating oils greatly increases the TFA content. In comparison, Chinese cuisine involves mostly braising, steaming, and boiling rather than frying. We hypothesize that South Asians' susceptibility to CHD is partly attributable to high-heat treated foods producing high NFCs. Research to accrue direct evidence is proposed. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Social Immunity: Emergence and Evolution of Colony-Level Disease Protection.

    Science.gov (United States)

    Cremer, Sylvia; Pull, Christopher D; Fürst, Matthias A

    2018-01-07

    Social insect colonies have evolved many collectively performed adaptations that reduce the impact of infectious disease and that are expected to maximize their fitness. This colony-level protection is termed social immunity, and it enhances the health and survival of the colony. In this review, we address how social immunity emerges from its mechanistic components to produce colony-level disease avoidance, resistance, and tolerance. To understand the evolutionary causes and consequences of social immunity, we highlight the need for studies that evaluate the effects of social immunity on colony fitness. We discuss the roles that host life history and ecology have on predicted eco-evolutionary dynamics, which differ among the social insect lineages. Throughout the review, we highlight current gaps in our knowledge and promising avenues for future research, which we hope will bring us closer to an integrated understanding of socio-eco-evo-immunology.

  10. Differential Disease Susceptibilities in Experimentally Reptarenavirus-Infected Boa Constrictors and Ball Pythons

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Garcia, Valentina E.; Layton, Marylee L.; Hoon-Hanks, Laura L.; Boback, Scott M.; Keel, M. Kevin; Drazenovich, Tracy

    2017-01-01

    .e., to identify organisms that appear to cause disease, but to be certain that a candidate pathogen actually causes disease, it is necessary to provide additional evidence of causality. We have done this to demonstrate that reptarenaviruses cause inclusion body disease (IBD), a serious transmissible disease of snakes. We infected boa constrictors and ball pythons with purified reptarenavirus. Ball pythons fell ill within 2 months of infection and displayed signs of neurological disease typical of IBD. In contrast, boa constrictors remained healthy over 2 years, despite high levels of virus throughout their bodies. This difference matches previous reports that pythons are more susceptible to IBD than boas and could reflect the possibility that boas are natural hosts of these viruses in the wild. PMID:28515291

  11. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

    DEFF Research Database (Denmark)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S

    2018-01-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns...... the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes...... in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely...

  12. Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

    Science.gov (United States)

    Jafri, Salema; Ormiston, Mark L

    2017-12-01

    Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4 + helper T cell populations, defined by excessive Th17 responses and impaired T reg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8 + T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders. Copyright © 2017 the American Physiological Society.

  13. Effect of ionizing radiation on humoral and cellular immunity in pigs vaccinated against Aujeszky's disease

    International Nuclear Information System (INIS)

    Bartoszcze, M.; Roszkowski, J.

    1991-01-01

    An effect of ionizing radiation on the immune response in pigs of both sexes weighing 35 kg vaccinated with an attenuated Aujeszky's disease virus was investigated. Ionizing radiation in a dose of 200 or 400 r reduced the number of IgM and IgG antibodies produced in vaccinated pigs. Additionally, the 400 r dose delyed the cellular immune response. No effect of the radiation on a clinical course of postvaccinal reaction was found

  14. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

    Science.gov (United States)

    Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

    2009-12-01

    While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

  15. Immune dysfunction in Niemann?Pick disease type C

    OpenAIRE

    Platt, Nick; Speak, Annelise O.; Colaco, Alexandria; Gray, James; Smith, David A.; Williams, Ian M.; Wallom, Kerri?Lee; Platt, Frances M.

    2015-01-01

    Abstract Lysosomal storage diseases are inherited monogenic disorders in which lysosome function is compromised. Although individually very rare, they occur at a collective frequency of approximately one in five thousand live births and usually have catastrophic consequences for health. The lysosomal storage diseases Niemann?Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral membrane protein NPC1 and clinically presents as a progressive neurodegenerative ...

  16. Detection of Marek's disease virus DNA in Japanese quail susceptible to atherosclerosis

    International Nuclear Information System (INIS)

    Pyrzak, R.; Shih, J.C.H.

    1986-01-01

    Marek's disease virus (MDV) was demonstrated as an etiological agent which causes atherosclerosis in the chicken. Since herpes viruses are ubiquitous, incidences of viral atherogenesis in humans and other animals were speculated. In this laboratory, the atherosclerosis susceptible (SUS) and resistant (RES) Japanese quail were developed as the animal model for atherosclerosis research. The susceptibility of the animal might be due to an infection of MDV or a related quail herpes virus (QHV). An initial attempt to isolate viruses from quail and an agar gel precipitin test for MDC were not positive. A DNA hybridization technique was used to determine whether the MDC-DNA existed in the quail cell. The gene library of MDV EcoRl DNA fragments was used to prepare the DNA probe, labeled with [ 32 P] by nick translation. Dot hybridizations were carried out by mixing the MDV-DNA probe with DNAs isolated from quail tissues. A high stringent condition was used. From this experiment it was found that the tissues from the SUS quail were hybridization positive, but most of them from RES quail were negative. When aortas were compared, the severe atherosclerotic had a strong hybridization (3-4 cop. of genome/cell) whereas the others hybridized moderately (1 cop./cell). It was concluded that genes from MDV or a QHV indeed existed in Japanese quail

  17. Association between Toll-like receptor 4 Asp299Gly polymorphism and coronary heart disease susceptibility.

    Science.gov (United States)

    Wu, B W; Zhu, J; Shi, H M; Jin, B; Wen, Z C

    2017-08-07

    Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.

  18. The immune response to Prevotella bacteria in chronic inflammatory disease

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura

    2017-01-01

    the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation....... Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella...... and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic inflammation....

  19. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  20. A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease.

    Science.gov (United States)

    Biemans, Floor; de Jong, Mart C M; Bijma, Piter

    2017-06-30

    Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of (genetic) traits: host susceptibility and host infectivity. Quantitative genetic studies on infectious diseases generally connect an individual's disease status to its own genotype, and therefore capture genetic effects on susceptibility only. However, they usually ignore variation in exposure to infectious herd mates, which may limit the accuracy of estimates of genetic effects on susceptibility. Moreover, genetic effects on infectivity will exist as well. Thus, to design optimal breeding strategies, it is essential that genetic effects on infectivity are quantified. Given the potential importance of genetic effects on infectivity, we set out to develop a model to estimate the effect of single nucleotide polymorphisms (SNPs) on both host susceptibility and host infectivity. To evaluate the quality of the resulting SNP effect estimates, we simulated an endemic disease in 10 groups of 100 individuals, and recorded time-series data on individual disease status. We quantified bias and precision of the estimates for different sizes of SNP effects, and identified the optimum recording interval when the number of records is limited. We present a generalized linear mixed model to estimate the effect of SNPs on both host susceptibility and host infectivity. SNP effects were on average slightly underestimated, i.e. estimates were conservative. Estimates were less precise for infectivity than for susceptibility. Given our sample size, the power to estimate SNP effects for susceptibility was 100% for differences between genotypes of a factor 1.56 or more, and was higher than 60% for infectivity for differences between genotypes of a factor 4 or more. When disease status was recorded 11 times on each

  1. Up in arms: Immune and nervous system response to sea star wasting disease

    Science.gov (United States)

    Fuess, Lauren E; Eiselord, Morgan E.; Closek, Collin J.; Tracy, Allison M.; Mauntz, Ruth; Gignoux-Wolfsohn, Sarah; Moritsch, Monica M; Yoshioka, Reyn; Burge, Colleen A.; Harvell, Drew; Friedman, Carolyn S.; Hershberger, Paul K.; Roberts, Steven B.

    2015-01-01

    Echinoderms, positioned taxonomically at the base of deuterostomes, provide an important system for the study of the evolution of the immune system. However, there is little known about the cellular components and genes associated with echinoderm immunity. The 2013–2014 sea star wasting disease outbreak is an emergent, rapidly spreading disease, which has led to large population declines of asteroids in the North American Pacific. While evidence suggests that the signs of this disease, twisting arms and lesions, may be attributed to a viral infection, the host response to infection is still poorly understood. In order to examine transcriptional responses of the sea star Pycnopodia helianthoides to sea star wasting disease, we injected a viral sized fraction (0.2 μm) homogenate prepared from symptomatic P. helianthoides into apparently healthy stars. Nine days following injection, when all stars were displaying signs of the disease, specimens were sacrificed and coelomocytes were extracted for RNA-seq analyses. A number of immune genes, including those involved in Toll signaling pathways, complement cascade, melanization response, and arachidonic acid metabolism, were differentially expressed. Furthermore, genes involved in nervous system processes and tissue remodeling were also differentially expressed, pointing to transcriptional changes underlying the signs of sea star wasting disease. The genomic resources presented here not only increase understanding of host response to sea star wasting disease, but also provide greater insight into the mechanisms underlying immune function in echinoderms.

  2. Molecules at the interface of Cryptococcus and the host that determine disease susceptibility.

    Science.gov (United States)

    Wozniak, Karen L; Olszewski, Michal A; Wormley, Floyd L

    2015-05-01

    Cryptococcus neoformans and Cryptococcus gattii, the predominant etiological agents of cryptococcosis, are fungal pathogens that cause disease ranging from a mild pneumonia to life-threatening infections of the central nervous system (CNS). Resolution or exacerbation of Cryptococcus infection is determined following complex interactions of several host and pathogen derived factors. Alternatively, interactions between the host and pathogen may end in an impasse resulting in the establishment of a sub-clinical Cryptococcus infection. The current review addresses the delicate interaction between the host and Cryptococcus-derived molecules that determine resistance or susceptibility to infection. An emphasis will be placed on data highlighted at the recent 9th International Conference on Cryptococcus and Cryptococcosis (ICCC). Copyright © 2015. Published by Elsevier Inc.

  3. Mud crab susceptibility to disease from white spot syndrome virus is species-dependent

    Directory of Open Access Journals (Sweden)

    Sritunyalucksana Kallaya

    2010-11-01

    Full Text Available Abstract Background Based on a report for one species (Scylla serrata, it is widely believed that mud crabs are relatively resistant to disease caused by white spot syndrome virus (WSSV. We tested this hypothesis by determining the degree of susceptibility in two species of mud crabs, Scylla olivacea and Scylla paramamosain, both of which were identified by mitochondrial 16 S ribosomal gene analysis. We compared single-dose and serial-dose WSSV challenges on S. olivacea and S. paramamosain. Findings In a preliminary test using S. olivacea alone, a dose of 1 × 106 WSSV copies/g gave 100% mortality within 7 days. In a subsequent test, 17 S. olivacea and 13 S. paramamosain were divided into test and control groups for challenge with WSSV at 5 incremental, biweekly doses starting from 1 × 104 and ending at 5 × 106 copies/g. For 11 S. olivacea challenged, 3 specimens died at doses between 1 × 105 and 5 × 105 copies/g and none died for 2 weeks after the subsequent dose (1 × 106 copies/g that was lethal within 7 days in the preliminary test. However, after the final challenge on day 56 (5 × 106 copies/g, the remaining 7 of 11 S. olivacea (63.64% died within 2 weeks. There was no mortality in the buffer-injected control crabs. For 9 S. paramamosain challenged in the same way, 5 (55.56% died after challenge doses between 1 × 104 and 5 × 105 copies/g, and none died for 2 weeks after the challenge dose of 1 × 106 copies/g. After the final challenge (5 × 106 copies/g on day 56, no S. paramamosain died during 2 weeks after the challenge, and 2 of 9 WSSV-infected S. paramamosain (22.22% remained alive together with the control crabs until the end of the test on day 106. Viral loads in these survivors were low when compared to those in the moribund crabs. Conclusions S. olivacea and S. paramamosain show wide variation in response to challenge with WSSV. S. olivacea and S. paramamosain are susceptible to white spot disease, and S. olivacea is more

  4. Differences in the susceptibility of dromedary and Bactrian camels to foot-and-mouth disease virus

    DEFF Research Database (Denmark)

    Larska, M.; Wernery, U.; Kinne, J.

    2009-01-01

    In this study, two sheep, eight dromedary camels and two Bactrian camels were inoculated with foot-and-mouth disease virus (FMDV) type A SAU 22/92. Five naive dromedary camels and four sheep were kept in direct or indirect contact with the inoculated camels. The inoculated sheep, which served...... as positive controls, displayed typical moderate clinical signs of FMD and developed viraemia and high antibody titres. The presence of the virus was also detected in probang and mouth-swab samples for several days after inoculation. In contrast, the inoculated dromedary camels were not susceptible to FMDV...... type A infection. None of them showed clinical signs of FMD or developed viraemia or specific anti-FMDV antibodies despite the high dose of virus inoculated. All the contact sheep and contact dromedaries that were kept together with the inoculated camels remained virus-negative and did not seroconvert...

  5. Efficacy of Spirulina platensis diet supplements on disease resistance and immune-related gene expression in Cyprinus carpio L. exposed to herbicide atrazine.

    Science.gov (United States)

    Khalil, Samah R; Reda, Rasha M; Awad, Ashraf

    2017-08-01

    The present study evaluated the immunotoxicological effects of the herbicide atrazine (ATZ) at sub-lethal concentrations and the potential ameliorative influence of Spirulina platensis (SP) over a sub-chronic exposure period on Cyprinus carpio L., also known as common carp. Common carp was sampled after a 40-days exposure to ATZ (428 μg/L) and SP (1%), individually or in combination to assess the non-specific immune response, changes in mRNA expression of immune-related genes [lysozyme (LYZ), immunoglobulin M (IgM), and complement component 3 (C3)] in the spleen, and inflammatory cytokines (interleukins IL-1ß and IL-10) in the head kidney using real-time PCR. Additionally, disease resistance to Aeromonas sobria was evaluated. The results revealed that ATZ exposure caused a significant decline in most of the hematological variables, lymphocyte viability, and lysozyme and bactericidal activity. Moreover, ATZ increased the susceptibility to disease, reflected by a significantly lower post-challenge survival rate of the carp. ATZ may induce dysregulated expression of immune-related genes leading to downregulation of mRNA levels of IgM and LYZ in the spleen. However, expression of C3 remained unaffected. Of the cytokine-related genes examined, IL-1B was up-regulated in the head kidney. In contrast, the expression of IL-10 gene was down-regulated in the ATZ-exposed group. The SP supplementation resulted in a significant improvement in most indices; however, these values did not match with that of the controls. These results may conclude that ATZ affects both innate and adaptive immune responses through the negative transcriptional effect on genes involved in immunity and also due to the inflammation of the immune organs. In addition, dietary supplements with SP could be useful for modulation of the immunity in response to ATZ exposure, thereby presenting a promising feed additive for carps in aquaculture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Identification of Two Additional Susceptibility Loci for Inflammatory Bowel Disease in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Xiucai Lan

    2017-04-01

    Full Text Available Background/Aims: To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1, rs1042522 (tumour protein p53, TP53, and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A polymorphisms and the development of inflammatory bowel disease (IBD in a Chinese (Han population. We analysed the expression of genes that predispose patients to Crohn’s disease (CD and ulcerative colitis (UC. Methods: A total of 381 IBD patients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR. Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR, western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mouse dextran sulphate sodium (DSS-induced acute colitis model. Results: No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044. The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level. Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBD patients and DSS-treated mice. Conclusion: rs1250569 (ZMIZ1 and rs10114470 (TL1A are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was

  7. Immunization Documentation Practices and Vaccine-Preventable Disease Surveillance Capacity among Institutions of Higher Education in Indiana

    Science.gov (United States)

    Stevens, Taryn; Golwalkar, Mugdha

    2018-01-01

    ABSTRACTObjective: Complete and accurate documentation of immunization records and surveillance of disease transmission are critical to the public health response to outbreaks of communicable disease in institutions of higher education (IHEs). This study aims to describe immunization documentation practices and disease surveillance capacity among…

  8. Corals hosting symbiotic hydrozoans are less susceptible to predation and disease

    KAUST Repository

    Montano, Simone

    2017-12-20

    In spite of growing evidence that climate change may dramatically affect networks of interacting species, whether-and to what extent-ecological interactions can mediate species\\' responses to disturbances is an open question. Here we show how a largely overseen association such as that between hydrozoans and scleractinian corals could be possibly associated with a reduction in coral susceptibility to ever-increasing predator and disease outbreaks. We examined 2455 scleractinian colonies (from both Maldivian and the Saudi Arabian coral reefs) searching for non-random patterns in the occurrence of hydrozoans on corals showing signs of different health conditions (i.e. bleaching, algal overgrowth, corallivory and different coral diseases). We show that, after accounting for geographical, ecological and co-evolutionary factors, signs of disease and corallivory are significantly lower in coral colonies hosting hydrozoans than in hydrozoan-free ones. This finding has important implications for our understanding of the ecology of coral reefs, and for their conservation in the current scenario of global change, because it suggests that symbiotic hydrozoans may play an active role in protecting their scleractinian hosts from stresses induced by warming water temperatures.

  9. Differences in Rhodococcus equi Infections Based on Immune Status and Antibiotic Susceptibility of Clinical Isolates in a Case Series of 12 Patients and Cases in the Literature

    Science.gov (United States)

    Suzuki, Yasuhiro; Ribes, Julie A.; Thornton, Alice

    2016-01-01

    Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P antibiotics, preferably selected from vancomycin, imipenem, clarithromycin/azithromycin, ciprofloxacin, rifampin, or cotrimoxazole. Local antibiograms should be checked prior to using cotrimoxazole due to developing resistance. PMID:27631004

  10. Trade-offs in disease and bleaching susceptibility among two color morphs of the Hawaiian reef coral, Montipora capitata

    Science.gov (United States)

    Shore-Maggio, Amanda; Callahan, Sean M.; Aeby, Greta S.

    2018-06-01

    Two threats impacting coral reefs are bleaching and disease, and differential susceptibility to both exists among and within coral taxa. Bleaching resistance is commonly linked to the clade of endosymbiotic Symbiodinium, but may come at a cost to other biological traits. Montipora capitata is an Indo-Pacific reef-building coral with two color morphs, red and orange, which harbor different clades of Symbiodinium. We explored whether these color morphs displayed differences in bleaching/disease susceptibility and other biological traits (growth rate, reproductive output, and lipid content). We found a trade-off between disease and bleaching susceptibility. The orange morph had significantly higher disease prevalence, whereas the red morph had significantly higher bleaching prevalence. Thermal stress experiments found that bleaching and loss of photochemical efficiency occurred significantly faster in the red morph, but at normal temperatures, the red morph had a significantly higher growth rate. Higher abundance of the red morph in the field suggests that disease resistance is a more successful strategy in the absence of thermal stress events. The orange morph may better tolerate increases in sea temperatures, but may not persist due to decreased growth rate and increased disease susceptibility. Trade-offs in response to stressors highlight the need to consider local and global threats to coral reefs.

  11. The impact of strain-specific immunity on Lyme disease incidence is spatially heterogeneous.

    Science.gov (United States)

    Khatchikian, Camilo E; Nadelman, Robert B; Nowakowski, John; Schwartz, Ira; Wormser, Gary P; Brisson, Dustin

    2017-12-01

    Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne infection in the US. Recent studies have demonstrated that the incidence of human Lyme disease would have been even greater were it not for the presence of strain-specific immunity, which protects previously infected patients against subsequent infections by the same B. burgdorferi strain. Here, spatial heterogeneity is incorporated into epidemiological models to accurately estimate the impact of strain-specific immunity on human Lyme disease incidence. The estimated reduction in the number of Lyme disease cases is greater in epidemiologic models that explicitly include the spatial distribution of Lyme disease cases reported at the county level than those that utilize nationwide data. strain-specific immunity has the greatest epidemiologic impact in geographic areas with the highest Lyme disease incidence due to the greater proportion of people that have been previously infected and have developed strain-specific immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Immune biomarkers in the spectrum of childhood noncommunicable diseases

    NARCIS (Netherlands)

    Skevaki, Chrysanthi; Van Den Berg, Jolice; Jones, Nicholas; Garssen, Johan; Vuillermin, Peter; Levin, Michael; Landay, Alan; Renz, Harald; Calder, Philip C.; Thornton, Catherine A.

    2016-01-01

    A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or

  13. Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Kullo Iftikhar J

    2011-04-01

    Full Text Available Abstract Background We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. Methods From the database of genome-wide association studies (GWAS, we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels. We identified 292 SNPs in 270 genes associated with a disease or trait at P -8. As part of the Human Genome-Diversity Project (HGDP, 158 (54.1% of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, FST, was calculated to quantify differences in risk allele frequencies (RAFs among populations and geographic areas. Results Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global FST (0.1042 for 158 SNPs among the populations was not significantly higher than the mean global FST of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global FST (P FST of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. Conclusion Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.

  14. The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans.

    Directory of Open Access Journals (Sweden)

    Juan S Ruiz-Moreno

    2018-01-01

    Full Text Available The cyclic GMP-AMP synthase (cGAS-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs. In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection.ClinicalTrials.gov DRKS00005274, German Clinical Trials Register.

  15. The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans.

    Science.gov (United States)

    Ruiz-Moreno, Juan S; Hamann, Lutz; Shah, Javeed A; Verbon, Annelies; Mockenhaupt, Frank P; Puzianowska-Kuznicka, Monika; Naujoks, Jan; Sander, Leif E; Witzenrath, Martin; Cambier, John C; Suttorp, Norbert; Schumann, Ralf R; Jin, Lei; Hawn, Thomas R; Opitz, Bastian

    2018-01-01

    The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. ClinicalTrials.gov DRKS00005274, German Clinical Trials Register.

  16. The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans

    Science.gov (United States)

    Hamann, Lutz; Verbon, Annelies; Mockenhaupt, Frank P.; Puzianowska-Kuznicka, Monika; Naujoks, Jan; Sander, Leif E.; Witzenrath, Martin; Schumann, Ralf R.; Hawn, Thomas R.

    2018-01-01

    The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires’ disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires’ disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. Trial registration ClinicalTrials.gov DRKS00005274, German Clinical Trials Register PMID:29298342

  17. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schafer, C.; Schwarz, E.

    2008-01-01

    Aim: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development...... of ALD in animal experiments, the hypothesis of the present retrospective cross-sectional study was that gender-dependent (micro-) nutrient intake in patients with ALD may cause the higher susceptibility of women to this disease. Methods: In 210 patients (male: 158, female: 52) with different stages...

  18. Loss of function in Mlo orthologs reduces susceptibility of pepper and tomato to powdery mildew disease caused by Leveillula taurica.

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    Zheng Zheng

    Full Text Available Powdery mildew disease caused by Leveillula taurica is a serious fungal threat to greenhouse tomato and pepper production. In contrast to most powdery mildew species which are epiphytic, L. taurica is an endophytic fungus colonizing the mesophyll tissues of the leaf. In barley, Arabidopsis, tomato and pea, the correct functioning of specific homologues of the plant Mlo gene family has been found to be required for pathogenesis of epiphytic powdery mildew fungi. The aim of this study was to investigate the involvement of the Mlo genes in susceptibility to the endophytic fungus L. taurica. In tomato (Solanum lycopersicum, a loss-of-function mutation in the SlMlo1 gene results in resistance to powdery mildew disease caused by Oidium neolycopersici. When the tomato Slmlo1 mutant was inoculated with L. taurica in this study, it proved to be less susceptible compared to the control, S. lycopersicum cv. Moneymaker. Further, overexpression of SlMlo1 in the tomato Slmlo1 mutant enhanced susceptibility to L. taurica. In pepper, the CaMlo2 gene was isolated by applying a homology-based cloning approach. Compared to the previously identified CaMlo1 gene, the CaMlo2 gene is more similar to SlMlo1 as shown by phylogenetic analysis, and the expression of CaMlo2 is up-regulated at an earlier time point upon L. taurica infection. However, results of virus-induced gene silencing suggest that both CaMlo1 and CaMlo2 may be involved in the susceptibility of pepper to L. taurica. The fact that overexpression of CaMlo2 restored the susceptibility of the tomato Slmlo1 mutant to O. neolycopersici and increased its susceptibility to L. taurica confirmed the role of CaMlo2 acting as a susceptibility factor to different powdery mildews, though the role of CaMlo1 as a co-factor for susceptibility cannot be excluded.

  19. The Microbiota Regulates Immunity and Immunologic Diseases in Dogs and Cats.

    Science.gov (United States)

    Tizard, Ian R; Jones, Sydney W

    2018-03-01

    The complex commensal microbiota found on body surfaces controls immune responses and the development of allergic and inflammatory diseases. New genetic technologies permit investigators to determine the composition of the complex microbial populations found on these surfaces. Changes in the microbiota (dysbiosis) as a result of antibiotic use, diet, or other factors thus influence the development of many diseases in the dog and cat. The most important of these include chronic gastrointestinal disease; respiratory allergies, such as asthma; skin diseases, especially atopic dermatitis; and some autoimmune diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. High-throughput Sequencing Based Immune Repertoire Study during Infectious Disease

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    Dongni Hou

    2016-08-01

    Full Text Available The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases that achieved by traditional techniques and high-throughput sequencing techniques. High-throughput sequencing techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge, and also provides a basis for further development of novel diagnostic markers, immunotherapies and vaccines.

  1. Routine Immunization of Adults in Canada: Review of the Epidemiology of Vaccine-Preventable Diseases and Current Recommendations for Primary Prevention

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    Michael D Parkins

    2009-01-01

    Full Text Available Vaccination is one of the greatest achievements in public health of the 20th century. However, the success of vaccine uptake and adherence to immunization guidelines seen in pediatric populations has not been observed among adult Canadians. As a result of the disparity in susceptibility to vaccine-preventable disease, there has been an increasing shift of vaccine-preventable childhood diseases into adult populations. Accordingly, morbidity and mortality due to vaccine-preventable illnesses now occur disproportionately in adults. All Canadians, irrespective of age, should have immunity to measles, mumps, rubella, tetanus, diphtheria, pertussis and varicella. All adult Canadians with significant medical comorbidities or those older than 65 years of age should receive the pneumococcal polysaccharide vaccine and yearly trivalent inactivate influenza vaccines. The present review summarizes the burden of illness of these vaccine-preventable diseases in the Canadian adult population and reviews the current immunization recommendations. Vaccination of all Canadians to these common agents remains a vital tool to decrease individual morbidity and mortality and reduce the overall burden of preventable disease in Canada.

  2. Immune defenses of healthy, bleached and diseased Montastraea faveolata during a natural bleaching event.

    Science.gov (United States)

    Mydlarz, Laura D; Couch, Courtney S; Weil, Ernesto; Smith, Garriet; Harvell, C Drew

    2009-11-16

    One prominent hypothesis regarding climate change and scleractinian corals is that thermal stress compromises immune competence. To test this hypothesis we tracked how the immune defenses of bleached, apparently healthy and yellow band disease (YBD) diseased Montastraea faveolata colonies varied with natural thermal stress in southwestern Puerto Rico. Colonies were monitored for 21 mo from the peak of the bleaching event in October 2005 to August 2007. Since sea surface temperature was significantly higher in summer and fall 2005 than 2006, year of collection was used as a proxy for temperature stress, and colony fragments collected in 2005 were compared with those collected in 2006. Mortality rate was high (43% overall) and all colonies (except one) either died or became infected with YBD by August 2007. YBD-infected tissue did not bleach (i.e. expel zooxanthellae) during the 2005 bleaching event, even when healthy tissue of these colonies bleached. Immune activity was assayed by measuring prophenoloxidase (PPO), peroxidase (POX), lysozyme-like (LYS) and antibacterial (AB) activity. Immune activity was variable between all coral samples, but there was a significant elevation of PPO activity in bleached colonies collected in 2005 relative to apparently healthy and YBD-diseased corals in 2006. In YBD-diseased colonies, LYS and AB activity were elevated in both healthy and infected tissue, indicating a systemic response; activity levels in these colonies were higher compared to those that appeared healthy. In both these immune parameters, there was a trend for suppression of activity in corals that were bleached in 2005. These data, while complicated by between-genet variability, illustrate the complex interaction between disease and temperature stress on immune function.

  3. CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

    Science.gov (United States)

    Alcina, Antonio; Teruel, María; Díaz-Gallo, Lina M.; Gómez-García, María; López-Nevot, Miguel A.; Rodrigo, Luis; Nieto, Antonio; Cardeña, Carlos; Alcain, Guillermo; Díaz-Rubio, Manuel; de la Concha, Emilio G.; Fernandez, Oscar; Arroyo, Rafael

    2010-01-01

    Background A functional polymorphism located at −1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions. Methodology Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93–1.17)]. Conclusion The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions. PMID:20634952

  4. Disease susceptibility of the human macula: differential gene transcription in the retinal pigmented epithelium/choroid.

    Science.gov (United States)

    Radeke, Monte J; Peterson, Katie E; Johnson, Lincoln V; Anderson, Don H

    2007-09-01

    The discoveries of gene variants associated with macular diseases have provided valuable insight into their molecular mechanisms, but they have not clarified why the macula is particularly vulnerable to degenerative disease. Its predisposition may be attributable to specialized structural features and/or functional properties of the underlying macular RPE/choroid. To examine the molecular basis for the macula's disease susceptibility, we compared the gene expression profile of the human RPE/choroid in the macula with the profile in the extramacular region using DNA microarrays. Seventy-five candidate genes with differences in macular:extramacular expression levels were identified by microarray analysis, of which 29 were selected for further analysis. Quantitative PCR confirmed that 21 showed statistically significant differences in expression. Five genes were expressed at higher levels in the macula. Two showed significant changes in the macular:extramacular expression ratio; another two exhibited changes in absolute expression level, as a function of age or AMD. Several of the differentially expressed genes have potential relevance to AMD pathobiology. One is an RPE cell growth factor (TFPI2), five are extracellular matrix components (DCN, MYOC, OGN, SMOC2, TFPI2), and six are related to inflammation (CCL19, CCL26, CXCL14, SLIT2) and/or angiogenesis (CXCL14, SLIT2, TFPI2, WFDC1). The identification of regional differences in gene expression in the RPE/choroid is a first step in clarifying the macula's propensity for degeneration. These findings lay the groundwork for further studies into the roles of the corresponding gene products in the normal, aged, and diseased macula.

  5. Estimating the total number of susceptibility variants underlying complex diseases from genome-wide association studies.

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    Hon-Cheong So

    2010-11-01

    Full Text Available Recently genome-wide association studies (GWAS have identified numerous susceptibility variants for complex diseases. In this study we proposed several approaches to estimate the total number of variants underlying these diseases. We assume that the variance explained by genetic markers (Vg follow an exponential distribution, which is justified by previous studies on theories of adaptation. Our aim is to fit the observed distribution of Vg from GWAS to its theoretical distribution. The number of variants is obtained by the heritability divided by the estimated mean of the exponential distribution. In practice, due to limited sample sizes, there is insufficient power to detect variants with small effects. Therefore the power was taken into account in fitting. Besides considering the most significant variants, we also tried to relax the significance threshold, allowing more markers to be fitted. The effects of false positive variants were removed by considering the local false discovery rates. In addition, we developed an alternative approach by directly fitting the z-statistics from GWAS to its theoretical distribution. In all cases, the "winner's curse" effect was corrected analytically. Confidence intervals were also derived. Simulations were performed to compare and verify the performance of different estimators (which incorporates various means of winner's curse correction and the coverage of the proposed analytic confidence intervals. Our methodology only requires summary statistics and is able to handle both binary and continuous traits. Finally we applied the methods to a few real disease examples (lipid traits, type 2 diabetes and Crohn's disease and estimated that hundreds to nearly a thousand variants underlie these traits.

  6. The Emerging Role of TLR and Innate Immunity in Cardiovascular Disease

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    Rolf Spirig

    2012-01-01

    Full Text Available Cardiovascular disease is a complex disorder involving multiple pathophysiological processes, several of which involve activation of toll-like receptors (TLRs of the innate immune system. As sentinels of innate immunity TLRs are nonclonally germline-encoded molecular pattern recognition receptors that recognize exogenous as well as tissue-derived molecular dangers signals promoting inflammation. In addition to their expression in immune cells, TLRs are found in other tissues and cell types including cardiomyocytes, endothelial and vascular smooth muscle cells. TLRs are differentially regulated in various cell types by several cardiovascular risk factors such as hypercholesterolemia, hyperlipidemia, and hyperglycemia and may represent a key mechanism linking chronic inflammation, cardiovascular disease progression, and activation of the immune system. Modulation of TLR signaling by specific TLR agonists or antagonists, alone or in combination, may be a useful therapeutic approach to treat various cardiovascular inflammatory conditions such as atherosclerosis, peripheral arterial disease, secondary microvascular complications of diabetes, autoimmune disease, and ischemia reperfusion injury. In this paper we discuss recent developments and current evidence for the role of TLR in cardiovascular disease as well as the therapeutic potential of various compounds on inhibition of TLR-mediated inflammatory responses.

  7. A Mathematical Model of Skeletal Muscle Disease and Immune Response in the mdx Mouse

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    Abdul Salam Jarrah

    2014-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.

  8. Genetic Predictions of Prion Disease Susceptibility in Carnivore Species Based on Variability of the Prion Gene Coding Region

    Science.gov (United States)

    Stewart, Paula; Campbell, Lauren; Skogtvedt, Susan; Griffin, Karen A.; Arnemo, Jon M.; Tryland, Morten; Girling, Simon; Miller, Michael W.; Tranulis, Michael A.; Goldmann, Wilfred

    2012-01-01

    Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrPC) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrPC protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter. PMID:23236380

  9. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

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    Paula Stewart

    Full Text Available Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE during the bovine spongiform encephalopathy (BSE epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD remains an open question. Variation in the host-encoded prion protein (PrP(C largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo and pine marten (Martes martes were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus and mountain lion (Puma concolor from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  10. Feasibility of the salivary transcriptome as a novel biomarker in determining disease susceptibility.

    Science.gov (United States)

    Hidayat, M F H; Milne, T; Cullinan, M P; Seymour, G J

    2018-06-01

    The salivary transcriptome may present as a readily available and non-invasive source of potential biomarkers. The development of chronic periodontitis is determined by individual patient susceptibility; hence, the aim of this study was to determine the potential of the salivary transcriptome as a biomarker of disease susceptibility using chronic periodontitis as an example. Using an Oragene ® RNA kit, the total RNA was purified from the saliva of 10 patients with chronic periodontitis and 10 patients without chronic periodontitis. The quantity and quality of the total RNA was determined, and a measure of gene expression via cDNA was undertaken using the Affymetrix microarray system. The microarray profiling result was further validated by real-time quantitative polymerase chain reaction. Spectrophotometric analysis showed the total RNA purified from each participant ranged from 0.92 μg/500 μL to 62.85 μg/500 μL. There was great variability in the quantity of total RNA obtained from the 2 groups in the study with a mean of 10.21 ± 12.71 μg/500 μL for the periodontitis group and 15.97 ± 23.47 μg/500 μL for the control group. Further the RNA purity (based on the A 260 /A 280 ratio) for the majority of participants (9 periodontitis and 6 controls) were within the acceptable limits for downstream analysis (2.0 ± 0.1). The study samples, showed 2 distinct bands at 23S (3800 bp) and 16S (1500 bp) characteristic of bacterial rRNA. Preliminary microarray analysis was performed for 4 samples (P2, P6, H5 and H9). The percentage of genes present in each of the 4 samples was not consistent with about 1.8%-18.7% of genes being detected. Quantitative real-time polymerase chain reaction confirmed that the total RNA purified from each sample was mainly bacterial RNA (Uni 16S) with minimal human mRNA. This study showed that minimal amounts of human RNA were able to be isolated from the saliva of patients with periodontitis as well as controls. Further

  11. Enriched Housing Reduces Disease Susceptibility to Co-Infection with Porcine Reproductive and Respiratory Virus (PRRSV) and Actinobacillus pleuropneumoniae (A. pleuropneumoniae) in Young Pigs.

    Science.gov (United States)

    van Dixhoorn, Ingrid D E; Reimert, Inonge; Middelkoop, Jenny; Bolhuis, J Elizabeth; Wisselink, Henk J; Groot Koerkamp, Peter W G; Kemp, Bas; Stockhofe-Zurwieden, Norbert

    2016-01-01

    Until today, anti-microbial drugs have been the therapy of choice to combat bacterial diseases. Resistance against antibiotics is of growing concern in man and animals. Stress, caused by demanding environmental conditions, can reduce immune protection in the host, influencing the onset and outcome of infectious diseases. Therefore psychoneuro-immunological intervention may prove to be a successful approach to diminish the impact of diseases and antibiotics use. This study was designed to investigate the effect of social and environmental enrichment on the impact of disease, referred to as "disease susceptibility", in pigs using a co-infection model of PRRSV and A. pleuropneumoniae. Twenty-eight pigs were raised in four pens under barren conditions and twenty-eight other pigs were raised in four pens under enriched conditions. In the enriched pens a combination of established social and environmental enrichment factors were introduced. Two pens of the barren (BH) and two pens of the enriched housed (EH) pigs were infected with PRRSV followed by A. pleuropneumoniae, the other two pens in each housing treatment served as control groups. We tested if differences in disease susceptibility in terms of pathological and clinical outcome were related to the different housing regimes and if this was reflected in differences in behavioural and immunological states of the animals. Enriched housed pigs showed a faster clearance of viral PRRSV RNA in blood serum (p = 0.014) and histologically 2.8 fold less interstitial pneumonia signs in the lungs (p = 0.014). More barren housed than enriched housed pigs developed lesions in the lungs (OR = 19.2, p = 0.048) and the lesions in the barren housed pigs showed a higher total pathologic tissue damage score (ppigs. EH pigs showed less stress-related behaviour and differed immunologically and clinically from BH pigs. We conclude that enriched housing management reduces disease susceptibility to co-infection of PRRSV and A

  12. Enriched Housing Reduces Disease Susceptibility to Co-Infection with Porcine Reproductive and Respiratory Virus (PRRSV and Actinobacillus pleuropneumoniae (A. pleuropneumoniae in Young Pigs.

    Directory of Open Access Journals (Sweden)

    Ingrid D E van Dixhoorn

    Full Text Available Until today, anti-microbial drugs have been the therapy of choice to combat bacterial diseases. Resistance against antibiotics is of growing concern in man and animals. Stress, caused by demanding environmental conditions, can reduce immune protection in the host, influencing the onset and outcome of infectious diseases. Therefore psychoneuro-immunological intervention may prove to be a successful approach to diminish the impact of diseases and antibiotics use. This study was designed to investigate the effect of social and environmental enrichment on the impact of disease, referred to as "disease susceptibility", in pigs using a co-infection model of PRRSV and A. pleuropneumoniae. Twenty-eight pigs were raised in four pens under barren conditions and twenty-eight other pigs were raised in four pens under enriched conditions. In the enriched pens a combination of established social and environmental enrichment factors were introduced. Two pens of the barren (BH and two pens of the enriched housed (EH pigs were infected with PRRSV followed by A. pleuropneumoniae, the other two pens in each housing treatment served as control groups. We tested if differences in disease susceptibility in terms of pathological and clinical outcome were related to the different housing regimes and if this was reflected in differences in behavioural and immunological states of the animals. Enriched housed pigs showed a faster clearance of viral PRRSV RNA in blood serum (p = 0.014 and histologically 2.8 fold less interstitial pneumonia signs in the lungs (p = 0.014. More barren housed than enriched housed pigs developed lesions in the lungs (OR = 19.2, p = 0.048 and the lesions in the barren housed pigs showed a higher total pathologic tissue damage score (p<0.001 than those in enriched housed pigs. EH pigs showed less stress-related behaviour and differed immunologically and clinically from BH pigs. We conclude that enriched housing management reduces disease

  13. Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases.

    Science.gov (United States)

    Oliveira, Marcio Sacramento de; Leon, Antônio Ponce de; Mattos, Inês Echenique; Koifman, Sérgio

    2011-09-01

    This study analyzed the association between air pollution and deaths from respiratory diseases, considering differential susceptibility according to gender. The authors used daily deaths from respiratory diseases (ICD-10, J00-J99), PM(10), SO(2), and O(3) levels, and meteorological indicators in Volta Redonda, Rio de Janeiro State, Brazil, from January 2002 to December 2006. The association was estimated by Poisson regression using generalized additive models, where the increase in risk of deaths from PM(10) to lag 1 was 10.01% (95%CI: 1.81-18.88%) in the total female population and 10.04% (95%CI: 0.90-20.02%) in elderly women. The increase in risk of deaths from PM(10) to lag 9 was 8.25% in the total male population (95%CI: 0.86-16.18%) and 10.80% (95%CI: 2.18-20.15%) in elderly men. For exposure to SO(2) and O(3), the risk was significant in the total male population and the elderly, respectively. The results emphasize the need for further studies, focusing on modification of the effects of air pollution on health.

  14. Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases

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    Marcio Sacramento de Oliveira

    2011-09-01

    Full Text Available This study analyzed the association between air pollution and deaths from respiratory diseases, considering differential susceptibility according to gender. The authors used daily deaths from respiratory diseases (ICD-10, J00-J99, PM10, SO2, and O3 levels, and meteorological indicators in Volta Redonda, Rio de Janeiro State, Brazil, from January 2002 to December 2006. The association was estimated by Poisson regression using generalized additive models, where the increase in risk of deaths from PM10 to lag 1 was 10.01% (95%CI: 1.81-18.88% in the total female population and 10.04% (95%CI: 0.90-20.02% in elderly women. The increase in risk of deaths from PM10 to lag 9 was 8.25% in the total male population (95%CI: 0.86-16.18% and 10.80% (95%CI: 2.18-20.15% in elderly men. For exposure to SO2 and O3, the risk was significant in the total male population and the elderly, respectively. The results emphasize the need for further studies, focusing on modification of the effects of air pollution on health.

  15. Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

    International Nuclear Information System (INIS)

    Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q.

    2014-01-01

    Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD

  16. Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q. [Department of Cardiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2014-08-08

    Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

  17. Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

    International Nuclear Information System (INIS)

    Fernandez-Cabezudo, Maria J.; Ali, Sumaya A.E.; Ullah, Azim; Hasan, Mohammed Y.; Kosanovic, Melita; Fahim, Mohamed A.; Adem, Abdu; Al-Ramadi, Basel K.

    2007-01-01

    Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for ∼ 16 weeks, resulting in a significant level of Pb in the blood (106.2 ± 8.9 μg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-γ and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions

  18. The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease.

    Science.gov (United States)

    Filyk, Heather A; Osborne, Lisa C

    2016-11-01

    Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Role of the peripheral innate immune system in the development of Alzheimer's disease.

    Science.gov (United States)

    Le Page, Aurélie; Dupuis, Gilles; Frost, Eric H; Larbi, Anis; Pawelec, Graham; Witkowski, Jacek M; Fulop, Tamas

    2017-12-21

    Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression. Microglia in the brain are innate immune cells, and brain-initiated inflammatory responses reflected in the periphery suggests that Alzheimer's disease is to some extent also a systemic inflammatory disease. Greater permeability of the blood brain barrier facilitates the transport of peripheral immune cells to the brain and vice versa so that a vicious circle originating on the periphery may contribute to the development of overt clinical AD. Persistent inflammatory challenges by pathogens in the periphery, increasing with age, may also contribute to the central propagation of the pathological changes seen clinically. Therefore, the activation status of peripheral innate immune cells may represent an early biomarker of the upcoming impact on the brain. The modulation of these cells may thus become a useful mechanism for modifying disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Cultivar Variation in Hormonal Balance Is a Significant Determinant of Disease Susceptibility to Xanthomonas campestris pv. campestris in Brassica napus

    Directory of Open Access Journals (Sweden)

    Md. Tabibul Islam

    2017-12-01

    Full Text Available This study aimed to directly elucidate cultivar variation in disease susceptibility and disease responses in relation to hormonal status in the interaction of Brassica napus cultivars and Xanthomonas campestris pv. campestris (Xcc, the causal agent of black rot disease. Fully expanded leaves of six B. napus cultivars (cvs. Capitol, Youngsan, Saturnin, Colosse, Tamra, and Mosa were inoculated with Xcc. At 14 days post-inoculation with Xcc, cultivar variation in susceptibility or resistance was interpreted with defense responses as estimated by redox status, defensive metabolites, and expression of phenylpropanoid synthesis-related genes in relation to endogenous hormonal status. Disease susceptibility of six cultivars was distinguished by necrotic lesions in the Xcc-inoculated leaves and characterized concurrently based on the higher increase in reactive oxygen species and lipid peroxidation. Among these cultivars, as the susceptibility was higher, the ratios of abscisic acid (ABA/jasmonic acid (JA and salicylic acid (SA/JA tended to increase with enhanced expression of SA signaling regulatory gene NPR1 and transcriptional factor TGA1 and antagonistic suppression of JA-regulated gene PDF 1.2. In the resistant cultivar (cv. Capitol, accumulation of defensive metabolites with enhanced expression of genes involved in flavonoids (chalcone synthase, proanthocyanidins (anthocyanidin reductase, and hydroxycinnamic acids (ferulate-5-hydroxylase biosynthesis and higher redox status were observed, whereas the opposite results were obtained for susceptible cultivars (cvs. Mosa and Tamra. These results clearly indicate that cultivar variation in susceptibility to infection by Xcc was determined by enhanced alteration of the SA/JA ratio, as a negative regulator of redox status and phenylpropanoid synthesis in the Brasica napus–Xcc pathosystem.

  1. Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

    Science.gov (United States)

    Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

    2015-03-01

    Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

  2. Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

    Science.gov (United States)

    Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

    2018-01-01

    Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection

    NARCIS (Netherlands)

    Anche, M.T.

    2016-01-01

    Mahlet Teka Anche. (2016). Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection. PhD thesis, Wageningen University, the Netherlands

    Genetic approaches aiming to reduce the prevalence of an infection in a

  4. New susceptibility loci associated with kidney disease in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Niina Sandholm

    2012-09-01

    Full Text Available Diabetic kidney disease, or diabetic nephropathy (DN, is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D. Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8 and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9. Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1 pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7, a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

  5. Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

    Science.gov (United States)

    Bergman, P; Seyedoleslami Esfahani, S; Engström, Y

    2017-01-01

    Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer. © 2017 Elsevier Inc. All rights reserved.

  6. Prenatal diethylstilbestrol exposure and self-reported immune-related diseases

    NARCIS (Netherlands)

    Vingerhoets, A. J.; Assies, J.; Goodkin, K.; van Heck, G. L.; Bekker, M. H.

    1998-01-01

    To compare self-reports of immune-related diseases in diethylstilbestrol (DES) daughters and controls. Prenatal exposure to DES has been associated with several malformations in the lower genital tract, a higher prevalence of adenosis, and increased risk of clear cell adenocarcinoma, and

  7. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

    NARCIS (Netherlands)

    Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)

    2012-01-01

    textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis

  8. Probiotics cultures in animal feed: Effects on ruminal fermentation, immune responses, and resistance to infectious diseases

    Science.gov (United States)

    We evaluated the effects of probiotics included in dairy cattle and mice feed on ruminal fermentation, immune responses, and resistance to Johne’s disease. To unveil the underlying mechanisms, dairy cattle were either fed Bovamine (1.04 x 10**9 cfu of Lactobacillus acidophilus NP51 plus 2.04 x 10**...

  9. Stress-induced modulation of the innate immune system in cardiovascular disease

    NARCIS (Netherlands)

    Lagraauw, Hendrik Maxime

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease in which lipids and cells of the immune system accumulate in the vessel wall. Clinical complications, such as a myocardial infarction or stroke may occur when advanced atherosclerotic lesions become unstable and rupture. In this thesis, the influence

  10. The role of nuclear medicine in the staging and management of human immune deficiency virus infection and associated diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ankrah, Alfred O.; Sathekge, Mike [Dept. of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria (South Africa); Glaudemans, Andor W. J. M.; Klein, Hans; Dierckx, Rudi A. J. O. [University of Groningen, University Medical Centre Groningen, Groningen (Netherlands)

    2017-06-15

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  11. The Role of Nuclear Medicine in the Staging and Management of Human Immune Deficiency Virus Infection and Associated Diseases.

    Science.gov (United States)

    Ankrah, Alfred O; Glaudemans, Andor W J M; Klein, Hans C; Dierckx, Rudi A J O; Sathekge, Mike

    2017-06-01

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  12. The role of nuclear medicine in the staging and management of human immune deficiency virus infection and associated diseases

    International Nuclear Information System (INIS)

    Ankrah, Alfred O.; Sathekge, Mike; Glaudemans, Andor W. J. M.; Klein, Hans; Dierckx, Rudi A. J. O.

    2017-01-01

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  13. Comparative analysis of the effectiveness of three immunization strategies in controlling disease outbreaks in realistic social networks.

    Directory of Open Access Journals (Sweden)

    Zhijing Xu

    Full Text Available The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies-acquaintance immunization, community-bridge immunization, and ring vaccination-were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures. However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice.

  14. Comparative analysis of the effectiveness of three immunization strategies in controlling disease outbreaks in realistic social networks.

    Science.gov (United States)

    Xu, Zhijing; Zu, Zhenghu; Zheng, Tao; Zhang, Wendou; Xu, Qing; Liu, Jinjie

    2014-01-01

    The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies-acquaintance immunization, community-bridge immunization, and ring vaccination-were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures). However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice.

  15. Oxidative Stress and Immune System in Vitiligo and Thyroid Diseases

    Science.gov (United States)

    Colucci, Roberta; Dragoni, Federica

    2015-01-01

    Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo. PMID:25838868

  16. Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?

    Science.gov (United States)

    Alcaïs, Alexandre; Quintana-Murci, Lluis; Thaler, David S; Schurr, Erwin; Abel, Laurent; Casanova, Jean-Laurent

    2010-12-01

    The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably among diseases and among studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline; (ii) theoretical modeling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age; (iii) available molecular evidence from both monogenic and complex genetics of infectious diseases in children and adults; (iv) current knowledge of immunity to primary and secondary or latent infections; (v) the state of the art in the clinical genetics of noninfectious pediatric and adult diseases; and (vi) evolutionary data for the genes underlying single-gene and complex disease risk. With the recent advent of new-generation deep resequencing, this model of single-gene variations underlying severe pediatric infectious diseases is experimentally testable. © 2010 New York Academy of Sciences.

  17. Acne: a new model of immune-mediated chronic inflammatory skin disease.

    Science.gov (United States)

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Caproni, M; Fabbri, P

    2015-04-01

    Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

  18. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  19. Rabbit haemorrhagic disease: advantages of cELISA in assessing immunity in wild rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Zheng, Tao; Parkes, John P

    2011-12-15

    Rabbit haemorrhagic disease (RHD) is an acute fatal disease of domestic and wild European rabbits (Oryctolagus cuniculus) caused by RHD virus (RHDV). Accurate assessment of immunity is of great importance for the conservation and control of wild rabbits. We evaluated a competitive ELISA (cELISA) against isotype ELISAs for assessing the protective immunity against the disease by challenging 50 wild-caught rabbits with a lethal dose of RHDV. Death or survival to the challenge was used as a criterion to determine the performance characteristics of the assay for the assessment of immunity in rabbits. At 1:10 dilution, a serum exhibiting ≥ 25% inhibition (1:10(25)) was regarded as the presence of RHDV-specific antibodies. Eleven of 16 (68.8%) rabbits with antibodies at 1:10(25) (<1:40) died of RHD. When the cut-off was moved from 25% to 50% inhibition (1:10(50)) at 1:10 serum dilution, the assay sensitivity, specificity and accuracy for the protective immunity were improved from 84%, 54.2% and 69.4% to 84%, 100% and 91.8%, respectively. We also demonstrated at the epitope amino acid sequence level why the presence of the RHDV-cross reactive benign rabbit calicivirus, which interfered with isotype ELISAs, had little impact on the specificity of the cELISA for the diagnosis of RHDV infection. The presence of RHDV-specific antibody at 1:10(50) by the cELISA is a reliable indicator for the protective immunity. In contrast to isotype ELISAs, the cELISA is a valuable specific tool for monitoring the herd immunity to RHD for the conservation and management of wild rabbits in the field. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  1. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  2. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  3. Homologues of CsLOB1 in citrus function as disease susceptibility genes in citrus canker.

    Science.gov (United States)

    Zhang, Junli; Huguet-Tapia, Jose Carlos; Hu, Yang; Jones, Jeffrey; Wang, Nian; Liu, Sanzhen; White, Frank F

    2017-08-01

    The lateral organ boundary domain (LBD) genes encode a group of plant-specific proteins that function as transcription factors in the regulation of plant growth and development. Citrus sinensis lateral organ boundary 1 (CsLOB1) is a member of the LBD family and functions as a disease susceptibility gene in citrus bacterial canker (CBC). Thirty-four LBD members have been identified from the Citrus sinensis genome. We assessed the potential for additional members of LBD genes in citrus to function as surrogates for CsLOB1 in CBC, and compared host gene expression on induction of different LBD genes. Using custom-designed transcription activator-like (TAL) effectors, two members of the same clade as CsLOB1, named CsLOB2 and CsLOB3, were found to be capable of functioning similarly to CsLOB1 in CBC. RNA sequencing and quantitative reverse transcription-polymerase chain reaction analyses revealed a set of cell wall metabolic genes that are associated with CsLOB1, CsLOB2 and CsLOB3 expression and may represent downstream genes involved in CBC. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  4. IMMUNOPATHOLOGIC SYNDROMES: IMMUNE AUTOAGGRESSION DISEASES, PATHOLOGIC TOLERANCE, «TRANSPLANT AGAINST HOST» REACTIONS

    Directory of Open Access Journals (Sweden)

    P.F. Litvitsky

    2007-01-01

    Full Text Available This publication is the fourth and last in the series of the brief lectures devoted to the role of the system, exercising the immunobiological supervision over the individual and continuous antigenic contents of the body both in normal conditions and in the event of the pathology. It reviews the etiology, pathogenesis and main manifestations of the immune auto aggression diseases, pathologic tolerance and «transplant against host» reactions.Key words: immune auto aggression, idiotype, antigenic mimicry, tolerance, «transplant against host» reactions.

  5. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.

    Science.gov (United States)

    Jenkins, Timothy G; Aston, Kenneth I; Pflueger, Christian; Cairns, Bradley R; Carrell, Douglas T

    2014-07-01

    Recent evidence demonstrates a role for paternal aging on offspring disease susceptibility. It is well established that various neuropsychiatric disorders (schizophrenia, autism, etc.), trinucleotide expansion associated diseases (myotonic dystrophy, Huntington's, etc.) and even some forms of cancer have increased incidence in the offspring of older fathers. Despite strong epidemiological evidence that these alterations are more common in offspring sired by older fathers, in most cases the mechanisms that drive these processes are unclear. However, it is commonly believed that epigenetics, and specifically DNA methylation alterations, likely play a role. In this study we have investigated the impact of aging on DNA methylation in mature human sperm. Using a methylation array approach we evaluated changes to sperm DNA methylation patterns in 17 fertile donors by comparing the sperm methylome of 2 samples collected from each individual 9-19 years apart. With this design we have identified 139 regions that are significantly and consistently hypomethylated with age and 8 regions that are significantly hypermethylated with age. A representative subset of these alterations have been confirmed in an independent cohort. A total of 117 genes are associated with these regions of methylation alterations (promoter or gene body). Intriguingly, a portion of the age-related changes in sperm DNA methylation are located at genes previously associated with schizophrenia and bipolar disorder. While our data does not establish a causative relationship, it does raise the possibility that the age-associated methylation of the candidate genes that we observe in sperm might contribute to the increased incidence of neuropsychiatric and other disorders in the offspring of older males. However, further study is required to determine whether, and to what extent, a causative relationship exists.

  6. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Directory of Open Access Journals (Sweden)

    Anna L Mitchell

    Full Text Available Autoimmune Addison's disease (AAD is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18, on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls. The data were analysed using a meta-analysis approach.In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7. A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  7. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Science.gov (United States)

    Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

    2015-01-01

    Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  8. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Timothy G Jenkins

    2014-07-01

    Full Text Available Recent evidence demonstrates a role for paternal aging on offspring disease susceptibility. It is well established that various neuropsychiatric disorders (schizophrenia, autism, etc., trinucleotide expansion associated diseases (myotonic dystrophy, Huntington's, etc. and even some forms of cancer have increased incidence in the offspring of older fathers. Despite strong epidemiological evidence that these alterations are more common in offspring sired by older fathers, in most cases the mechanisms that drive these processes are unclear. However, it is commonly believed that epigenetics, and specifically DNA methylation alterations, likely play a role. In this study we have investigated the impact of aging on DNA methylation in mature human sperm. Using a methylation array approach we evaluated changes to sperm DNA methylation patterns in 17 fertile donors by comparing the sperm methylome of 2 samples collected from each individual 9-19 years apart. With this design we have identified 139 regions that are significantly and consistently hypomethylated with age and 8 regions that are significantly hypermethylated with age. A representative subset of these alterations have been confirmed in an independent cohort. A total of 117 genes are associated with these regions of methylation alterations (promoter or gene body. Intriguingly, a portion of the age-related changes in sperm DNA methylation are located at genes previously associated with schizophrenia and bipolar disorder. While our data does not establish a causative relationship, it does raise the possibility that the age-associated methylation of the candidate genes that we observe in sperm might contribute to the increased incidence of neuropsychiatric and other disorders in the offspring of older males. However, further study is required to determine whether, and to what extent, a causative relationship exists.

  9. Large scale association analysis identifies three susceptibility loci for coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Saade

    Full Text Available Genome wide association studies (GWAS and their replications that have associated DNA variants with myocardial infarction (MI and/or coronary artery disease (CAD are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3, and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035, while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086. Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

  10. Multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations

    NARCIS (Netherlands)

    Einarsdottir, Elisabet; Bevova, Marianna R.; Zhernakova, Alexandra; Monsuur, Alienke; Koskinen, Lotta L. E.; van't Slot, Ruben; Mulder, Chris; Mearin, M. Luisa; Korponay-Szabo, Ilma R.; Kaukinen, Katri; Kurppa, Kalle; Kere, Juha; Maki, Markku; Wijmenga, Cisca; Saavalainen, Paivi

    Celiac disease is an inflammatory enteropathy caused by intolerance to gluten. Previous linkage studies in the Dutch, Finnish and Hungarian populations have revealed a locus on chromosome 6q21-22 conferring susceptibility to celiac disease. This locus has previously been implicated in susceptibility

  11. Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease.

    Science.gov (United States)

    Middeldorp, Jaap M

    2015-01-01

    Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

  12. SAP: structure, function, and its roles in immune-related diseases.

    Science.gov (United States)

    Xi, Dan; Luo, TianTian; Xiong, Haowei; Liu, Jichen; Lu, Hao; Li, Menghao; Hou, Yuqing; Guo, Zhigang

    2015-01-01

    Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Extracellular cell stress (heat shock) proteins-immune responses and disease: an overview.

    Science.gov (United States)

    Pockley, A Graham; Henderson, Brian

    2018-01-19

    Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory 'danger signals' for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. © 2017 The Author(s).

  14. Steroid sparing regimens for management of oral immune-mediated diseases

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    Arti Agrawal

    2014-01-01

    Full Text Available Immune-mediated mucocutaneous disease may present oral symptoms as a first sign of the disease. The primary etiology could be the cellular and/or humoral immune responses directed against epithelial or connective tissue, in a chronic and recurrent pattern. Lichen planus, pemphigus vulgaris and bullous pemphigoid are the most frequent immunologically mediated mucocutaneous diseases. More often than not, patients present with complaints of blisters, oral ulcers, pain, burning sensation, and bleeding from the various oral sites. Steroids, whether topical or systemic, are the treatment of choice as they have both anti-inflammatory and immune-suppressant properties; however, challenges in the treatment of autoimmune diseases are the complexity of symptoms, the need to manage long-term medications for preserving organ function, and the long-term adverse effects of steroids. In such situations steroid sparing agents, such as, tacrolimus, dapsone, azathioprine, cyclosporine, and so on, may be helpful. Here an attempt is made to review various treatment regimens that could be used as alternatives to steroids for management of such diseases.

  15. Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice.

    Science.gov (United States)

    Matsui, Mariko; Rouleau, Vincent; Bruyère-Ostells, Lilian; Goarant, Cyrille

    2011-11-01

    Leptospirosis is a widespread zoonosis characterized by multiple organ failure and variable host susceptibility toward pathogenic Leptospira strains. In this study, we put the role of inflammatory mediators in parallel with bacterial burdens and organ lesions by comparing a susceptible animal model, the hamster, and a resistant one, the Oncins France 1 (OF1) mouse, both infected with virulent Leptospira interrogans serovar Icterohaemorrhagiae strain Verdun. Histological observations evidenced edema, congestion, hemorrhage, and inflammatory infiltration in the organs of hamsters, in contrast to limited changes in mice. Using reverse transcription-quantitative PCR techniques, we showed that the relative Leptospira burden progressively increased in hamster tissues, while a rapid clearance was observed in mouse tissues. The early regulation of the proinflammatory mediators interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and cyclo-oxygenase-2 and the chemokines gamma interferon-inducible protein 10 kDa/CXCL10 and macrophage inflammatory protein-1α/CCL3 in mouse tissues contrasted with their delayed and massive overexpression in hamster tissues. Conversely, the induction of the anti-inflammatory cytokine IL-10 was faster in the resistant than in the susceptible animal model. The role of these cytokines in the pathophysiology of leptospirosis and the implications of their differential regulation in the development of this disease are discussed.

  16. Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

    Science.gov (United States)

    Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

    2016-06-01

    Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These

  17. Parental genetic diversity of brown trout (Salmo trutta m. fario) brood stock affects offspring susceptibility to whirling disease.

    Science.gov (United States)

    Eszterbauer, Edit; Forró, Barbara; Tolnai, Zoltán; Guti, Csaba Ferenc; Zsigmond, Gergely; Hoitsy, György; Kallert, Dennis Marc

    2015-03-03

    Whirling disease, caused by the myxozoan parasite Myxobolus cerebralis, has high economical and ecological importance worldwide. Susceptibility to the disease varies considerably among salmonid species. In brown trout (Salmo trutta) the infection is usually subclinical with low mortality, which increases the risk of parasite dissemination, especially when farm fish are used for stocking natural habitats. The influence of intraspecific genetic differences (especially the level of homozygosity) on susceptibility is unknown. Therefore, we examined the possible correlations between parental genetic diversity and offspring susceptibility of brown trout stocks to whirling disease. Two brown trout brood stocks from a German and a Hungarian fish farm were genetically characterized using microsatellite and lineage-specific genetic markers. The individual inbreeding coefficient f and pairwise relatedness factor r were estimated based on eight microsatellite markers. Brood stock populations were divided into groups according to low and high f and r value estimates and subjected to selective fertilization. The offspring from these separate groups were exposed to M. cerebralis actinospores, and the infection prevalence and intensity was measured and statistically analysed. The analysis of phylogeographic lineage heritage revealed high heterogeneity in the Hungarian brood stock since > 50% of individuals were Atlantic-Danubian hybrids, while only pure Atlantic-descending specimens were detected in the German population. Based on f msat and r msat estimations, classified non-inbred (NIB), inbred (IB) and a group of closely related fish (REL) were created. The susceptibility of their offspring varied considerably. Although there was no significant difference in the prevalence of M. cerebralis infection, the mean intensity of infection differed significantly between NIB and IB groups. In REL and IB groups, a high variability was observed in infection intensity. No external

  18. T-cell receptor variable genes and genetic susceptibility to celiac disease: an association and linkage study.

    Science.gov (United States)

    Roschmann, E; Wienker, T F; Gerok, W; Volk, B A

    1993-12-01

    Genetic susceptibility of celiac disease is primarily associated with a particular combination of and HLA-DQA1/DQB1 gene; however, this does not fully account for the genetic predisposition. Therefore, the aim of this study was to examine whether T-cell receptor (TCR) genes may be susceptibility genes in celiac disease. HLA class II typing was performed by polymerase chain reaction amplification in combination with sequence-specific oligonucleotide hybridization. TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were investigated by restriction fragment length polymorphism analysis. Allelic frequencies of TCRA, TCRG, and TCRB variable genes were compared between patients with celiac disease (n = 53) and control patients (n = 67), and relative risk (RR) estimates were calculated. The RR was 1.67 for allele C1 at TCRA1, 3.35 for allele D2 at TCRA2, 1.66 for allele B2 at TCRG, and 1.35 for allele B at TCRB, showing no significant association. Additionally, linkage analysis was performed in 23 families. The logarithm of odd scores for celiac disease vs. the TCR variable genes at TCRA, TCRG, and TCRB showed no significant linkage. These data suggest that the analyzed TCR variable gene segments V alpha 1.2, V gamma 11, and V beta 8 do not play a major role in susceptibility to celiac disease.

  19. Beyond retrograde and anterograde signalling: mitochondrial-nuclear interactions as a means for evolutionary adaptation and contemporary disease susceptibility.

    Science.gov (United States)

    Ballinger, Scott W

    2013-02-01

    Although there is general agreement that most forms of common disease develop as a consequence of a combination of factors, including genetic, environmental and behavioural contributors, the actual mechanistic basis of how these factors initiate or promote diabetes, cancer, neurodegenerative and cardiovascular diseases in some individuals but not in others with seemingly identical risk factor profiles, is not clearly understood. In this respect, consideration of the potential role for mitochondrial genetics, damage and function in influencing common disease susceptibility seems merited, given that the prehistoric challenges were the original factors that moulded cellular function, and these were based upon the mitochondrial-nuclear relationships that were established during evolutionary history. These interactions were probably refined during prehistoric environmental selection events that, at present, are largely absent. Contemporary risk factors such as diet, sedentary lifestyle and increased longevity, which influence our susceptibility to a variety of chronic diseases were not part of the dynamics that defined the processes of mitochondrial-nuclear interaction, and thus cell function. Consequently, the prehistoric challenges that contributed to cell functionality and evolution should be considered when interpreting and designing experimental data and strategies. Although several molecular epidemiological studies have generally supported this notion, studies that probe beyond these associations are required. Such investigation will mark the initial steps for mechanistically addressing the provocative concept that contemporary human disease susceptibility is the result of prehistoric selection events for mitochondrial-nuclear function, which increased the probability for survival and reproductive success during evolution.

  20. Genetic susceptibility, colony size, and water temperature drive white-pox disease on the coral Acropora palmata.

    Science.gov (United States)

    Muller, Erinn M; van Woesik, Robert

    2014-01-01

    Outbreaks of coral diseases are one of the greatest threats to reef corals in the Caribbean, yet the mechanisms that lead to coral diseases are still largely unknown. Here we examined the spatial-temporal dynamics of white-pox disease on Acropora palmata coral colonies of known genotypes. We took a Bayesian approach, using Integrated Nested Laplace Approximation algorithms, to examine which covariates influenced the presence of white-pox disease over seven years. We showed that colony size, genetic susceptibility of the coral host, and high-water temperatures were the primary tested variables that were positively associated with the presence of white-pox disease on A. palmata colonies. Our study also showed that neither distance from previously diseased individuals, nor colony location, influenced the dynamics of white-pox disease. These results suggest that white-pox disease was most likely a consequence of anomalously high water temperatures that selectively compromised the oldest colonies and the most susceptible coral genotypes.

  1. Genetic susceptibility, colony size, and water temperature drive white-pox disease on the coral Acropora palmata.

    Directory of Open Access Journals (Sweden)

    Erinn M Muller

    Full Text Available Outbreaks of coral diseases are one of the greatest threats to reef corals in the Caribbean, yet the mechanisms that lead to coral diseases are still largely unknown. Here we examined the spatial-temporal dynamics of white-pox disease on Acropora palmata coral colonies of known genotypes. We took a Bayesian approach, using Integrated Nested Laplace Approximation algorithms, to examine which covariates influenced the presence of white-pox disease over seven years. We showed that colony size, genetic susceptibility of the coral host, and high-water temperatures were the primary tested variables that were positively associated with the presence of white-pox disease on A. palmata colonies. Our study also showed that neither distance from previously diseased individuals, nor colony location, influenced the dynamics of white-pox disease. These results suggest that white-pox disease was most likely a consequence of anomalously high water temperatures that selectively compromised the oldest colonies and the most susceptible coral genotypes.

  2. Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

    Directory of Open Access Journals (Sweden)

    Ruth Pye

    2018-02-01

    Full Text Available Devil facial tumor disease (DFTD is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33, these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol® and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of

  3. Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

    Science.gov (United States)

    Pye, Ruth; Patchett, Amanda; McLennan, Elspeth; Thomson, Russell; Carver, Scott; Fox, Samantha; Pemberton, David; Kreiss, Alexandre; Baz Morelli, Adriana; Silva, Anabel; Pearse, Martin J.; Corcoran, Lynn M.; Belov, Katherine; Hogg, Carolyn J.; Woods, Gregory M; Lyons, A. Bruce

    2018-01-01

    Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti

  4. The immune system, natural autoantibodies and general homeostasis in health and disease.

    Science.gov (United States)

    Poletaev, A; Boura, P

    2011-10-01

    It is generally accepted that the destination of the immune system is not only to discriminate between self and non-self but also to mount responses against non-self. During the last decades, it became evident that weak self-reactivity is a necessary condition for immune homeostasis. Natural self reactivity and the internal image created by autoantibodies, participate greatly to the maintenance of homeostasis. Under conditions of increased or altered antigenic pressure, the homeostatic status is disrupted and the organism becomes vulnerable to the emergence of diseases. "Immunculus" is the self-reactive and interconnected entity of the immune system, provided by a complicated network of natural autoantibobies of different specificity, as a mosaic picture. Quantitative changes in each part of the image are related to variations of expression of relative antigens. The immune system takes in account image information from the continuous screening of the antigenic status and compares between presented state and the desired (optimal) one. Substantial and prolonged deviations from the optimal state, triggers the induction of compensatory and reparative processes, aiming to restore molecular and functional homeostasis. So, natural autoimmunity through the ability of natural a-Abs to induce mechanisms of natural and acquired immunity, aims to prevent pathogenic processes and maintain or restore health status.

  5. Innate Immunity and Saliva in Candida albicans–mediated Oral Diseases

    Science.gov (United States)

    Salvatori, O.; Puri, S.; Tati, S.; Edgerton, M.

    2016-01-01

    The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals. PMID:26747422

  6. Molecular aspects of plant disease susceptibility: Arabidopsis genes affecting downy mildew infection

    NARCIS (Netherlands)

    Lapin, D.

    2013-01-01

    Interactions of plants with pathogenic microorganisms are influenced by multiple biotic and abiotic factors. The host immune system can detect pathogens and restrict their growth and development, but also non-immunity related host factors and processes can contribute to pathogenesis by attracting

  7. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  8. Herd immunity to Newcastle disease virus in broiler flocks in Israel.

    Science.gov (United States)

    Wiseman, Anat; Berman, Elyakum M

    2017-08-01

    Due to the ongoing need to protect poultry from virulent Newcastle disease virus, all commercial poultry flocks in Israel are vaccinated according to a defined programme using a combination of live and inactivated vaccines. The vaccination protocol for broilers during the years of the study comprised a live vaccine administered by spray on the day of hatching, inactivated vaccine by subcutaneous injection at 10-12 days of age, and another live vaccine given by aerosol at 17-21 days of age. A cross-sectional study was designed in order to examine the influence of herd immunity on the risk of Newcastle disease outbreak in broiler flocks. The study was based on the extensive field data kept in the Poultry Health Laboratories database. The results of serology tests employing haemagglutination inhibition for Newcastle disease virus were analysed and crossed with the list of flocks that had been diagnosed with ND in the years 2007-2014. At the peak of induced immunization (fifth week of growth), 87.5% of the tested flocks had achieved herd immunity (≥85% of birds in the flock with an HI titre ≥4). Based on a logistic regression model, the odds ratio for ND in flocks without herd immunity was 3.7 (95% CI 1.8-7.3, P-value < 0.001). The higher the percentage of birds with low HI titres the higher the risk of ND outbreak. Under field conditions, herd immunity is an important indicator for the risk of ND outbreak.

  9. Harnessing what lies within: Programming immunity with biocompatible devices to treat human disease

    Science.gov (United States)

    Roberts, Reid Austin

    Advances in our mechanistic insight of cellular function and how this relates to host physiology have revealed a world which is intimately connected at the macro and micro level. Our increasing understanding of biology exemplifies this, where cells respond to environmental cues through interconnected networks of proteins which function as receptors and adaptors to elicit gene expression changes that drive appropriate cellular programs for a given stimulus. Consequently, our deeper molecular appreciation of host homeostasis implicates aberrations of these pathways in nearly all major human disease categories, including those of infectious, metabolic, neurologic, oncogenic, and autoimmune etiology. We have come to recognize the mammalian immune system as a common network hub among all these varied pathologies. As such, the major goal of this dissertation is to identify a platform to program immune responses in mammals so that we may enhance our ability to treat disease and improve health in the 21st century. Using advances in materials science, in particular a recently developed particle fabrication technology termed Particle Replication in Non-wetting Templates (PRINT), our studies systematically assess the murine and human immune response to precisely fabricated nano- and microscale particles composed of biodegradable and biocompatible materials. We then build on these findings and present particle design parameters to program a number of clinically attractive immune responses by targeting endogenous cellular signaling pathways. These include control of particle uptake through surface modification, design parameters that modulate the magnitude and kinetics of biological signaling dynamics that can be used to exacerbate or dampen inflammatory responses, as well as particle designs which may be of use in treating allergies and autoimmune disorders. In total, this dissertation provides evidence that rational design of biocompatible nano- and microparticles is a viable

  10. The immune response of Taiwan abalone Haliotis diversicolor supertexta and its susceptibility to Vibrio parahaemolyticus at different salinity levels.

    Science.gov (United States)

    Cheng, Winton; Juang, Feng-Ming; Chen, Jiann-Chu

    2004-03-01

    Addition of NaCl at 2.5% to 3.5% to tryptic soy broth (TSB) significantly increased the growth of Vibrio parahaemolyticus. Taiwan abalone Haliotis diversicolor supertexta held in 30 per thousand seawater were injected with V. parahaemolyticus grown in TSB containing NaCl at 0.5, 1.5, 2.5, 3.5 and 4.5% at a dose of 1.6 x 10(5)colony-forming units (cfu) abalone(-1). After 48 h, the cumulative mortality was significantly higher for the abalone challenged with V. parahaemolyticus grown in 2.5% than those grown in 0.5 and 1.5% NaCl. In other experiments, abalones held in 30 per thousand seawater were injected with TSB-grown V. parahaemolyticus (1.6 x 10(5)cfu abalone(-1)), and then transferred to 20, 25, 30 and 35 per thousand seawater. All abalones held in 20 per thousand were killed in 48 h. The mortality of V. parahaemolyticus-injected abalone held in 30 per thousand was significantly lower over 24-120 h. Abalone held in 30 per thousand seawater and then transferred to 20, 25, 30 and 35 per thousand were examined for THC (total haemocyte count), phenoloxidase activity, respiratory burst, phagocytic activity and clearance efficiency of V. parahemolyticus after 24 and 72 h. The THC increased directly related with salinity levels. Phenoloxidase activity, respiratory burst, phagocytic activity and clearance efficiency of V. parahaemolyticus decreased significantly for the abalone in 20, 25 and 35 per thousand. It is concluded that the abalone transferred from 30 per thousand to 20, 25 and 35 per thousand had reduced immune ability and decreased resistance against V. parahaemolyticus infection.

  11. Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

    Science.gov (United States)

    Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

    2014-01-30

    The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease?

    Science.gov (United States)

    Colbeck, Emily Jayne; Ager, Ann; Gallimore, Awen; Jones, Gareth Wyn

    2017-01-01

    Secondary lymphoid organs are integral to initiation and execution of adaptive immune responses. These organs provide a setting for interactions between antigen-specific lymphocytes and antigen-presenting cells recruited from local infected or inflamed tissues. Secondary lymphoid organs develop as a part of a genetically preprogrammed process during embryogenesis. However, organogenesis of secondary lymphoid tissues can also be recapitulated in adulthood during de novo lymphoid neogenesis of tertiary lymphoid structures (TLSs). These ectopic lymphoid-like structures form in the inflamed tissues afflicted by various pathological conditions, including cancer, autoimmunity, infection, or allograft rejection. Studies are beginning to shed light on the function of such structures in different disease settings, raising important questions regarding their contribution to progression or resolution of disease. Data show an association between the tumor-associated TLSs and a favorable prognosis in various types of human cancer, attracting the speculation that TLSs support effective local antitumor immune responses. However, definitive evidence for the role for TLSs in fostering immune responses in vivo are lacking, with current data remaining largely correlative by nature. In fact, some more recent studies have even demonstrated an immunosuppressive, tumor-promoting role for cancer-associated TLSs. In this review, we will discuss what is known about the development of cancer-associated TLSs and the current understanding of their potential role in the antitumor immune response. PMID:29312327

  13. Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.

    Science.gov (United States)

    Bertram, Lars; Lange, Christoph; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F; Schjeide, Brit M M; Hooli, Basavaraj; Divito, Jason; Ionita, Iuliana; Jiang, Hongyu; Laird, Nan; Moscarillo, Thomas; Ohlsen, Kari L; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Murphy, Amy; Wagner, Steven L; Blacker, Deborah; Becker, K David; Tanzi, Rudolph E

    2008-11-01

    Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN2(1-4)) or to increase susceptibility for late-onset AD (APOE5). However, the heritability of late-onset AD is as high as 80%, (6) and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 x 10(-14)) was elicited by SNP rs4420638 and probably reflects APOE-epsilon4, which maps 11 kb proximal (r2 = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of approximately 1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-epsilon4, primarily acts as a modifier of onset age.

  14. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

    Science.gov (United States)

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-01-01

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  15. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

    Science.gov (United States)

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-02-26

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  16. Utility of susceptibility-weighted MRI in differentiating Parkinson's disease and atypical parkinsonism

    International Nuclear Information System (INIS)

    Gupta, Deepak; Saini, Jitender; Kesavadas, Chandrasekharan; Sarma, P.S.; Kishore, Asha

    2010-01-01

    Neuropathological studies report varying patterns of brain mineralization in Parkinson's diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility-weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P. Eleven patients with PD, 12 with PSP, 12 with MSA-P, and 11 healthy controls underwent SWI of the brain. Hypointensity of putamen, red nucleus, substantia nigra, and dentate nucleus in all groups were measured using an objective grading scale and scored from 0 to 3. In PSP, hypointensity score of red nucleus was higher than that in MSA-P (p = 0.001) and PD (p = 0.001), and a score of ≥2 differentiated the PSP group from the PD and MSA-P groups. Putaminal hypointensity score was higher in PSP when compared to that in PD (p = 0.003), and a score of ≥2 differentiated PSP from PD groups. SWI hypointensity scores of red nucleus and putamen had an excellent intrarater and interrater correlation. Substantia nigra hypointensity score of the PSP group was higher than that of the MSA-P (p = 0.004) and PD (p = 0.006) groups, but the scores had only a moderate intrarater and interrater correlation. SWI shows different patterns of brain mineralization in clinically diagnosed groups of PD, PSP, and MSA-P and may be considered as an additional MR protocol to help differentiate these conditions. (orig.)

  17. Lung Transcriptome of Newcastle Disease Virus Infected Chickens--Different Immune Response in Two Types of Chicken

    Data.gov (United States)

    US Agency for International Development — Males and females from resistant Fayoumi and susceptible Leghorn chicken lines were either challenged with a lentogenic strain of Newcastle Disease virus or given a...

  18. Prostaglandin E and the local immune response in chronic periodontal disease

    International Nuclear Information System (INIS)

    Loening, T.; Albers, H.-K.; Lisboa, B.P.; Burkhardt, A.; Caselitz, J.

    1980-01-01

    The local immune reaction of progressive chronic periodontal disease may be particularly influenced by macrophages and macrophage-derived factors. Among these substances the prostaglandins and lysosomal enzymes may play an important pathogenetic role. Parallel immunohistochemical and radioimmunological studies were done to investigate the relatiships of the immune-competent cells and the inflammatory mediators in gingival tissues. The radioimmunological analysis revealed that prostaglandin E increases markedly in the established gingival lesions. Immunohistochemically prostaglandin E was mainly localized within macrophage-like cells. Cytoplasmic lysozyme could be detected in these cells, too. On the other hand, the B-cell response is the prominent feature in established chronic periodontal disease. However, there is apparently a disturbed B-cell reaction as indicated by the irregular IgG-subclass pattern and by the production of mainly monomeric IgA. The possible interactions of macrophages and especially B-cells via prostaglandin E-mediated mechanisms are discussed. (author)

  19. Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems

    Science.gov (United States)

    Dusi, Veronica; Ghidoni, Alice; Ravera, Alice; De Ferrari, Gaetano M.; Calvillo, Laura

    2016-01-01

    Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a “working-network” in deep linkage with the autonomic nervous system. In this paper we will describe the single chemokines more involved in heart diseases; then we will present a comprehensive perspective of them as a complex network connecting the cardiovascular system to both the immune and the autonomic nervous systems. Finally, some recent evidences indicating chemokines as a possible new tool to predict cardiovascular risk will be described. PMID:27242392

  20. Admixture mapping of end stage kidney disease genetic susceptibility using estimated mutual information ancestry informative markers

    Directory of Open Access Journals (Sweden)

    Geiger Dan

    2010-10-01

    Full Text Available Abstract Background The question of a genetic contribution to the higher prevalence and incidence of end stage kidney disease (ESKD among African Americans (AA remained unresolved, until recent findings using admixture mapping pointed to the association of a genomic locus on chromosome 22 with this disease phenotype. In the current study we utilize this example to demonstrate the utility of applying a multi-step admixture mapping approach. Methods A multi-step case only admixture mapping study, consisted of the following steps was designed: 1 Assembly of the sample dataset (ESKD AA; 2 Design of the estimated mutual information ancestry informative markers (n = 2016 screening panel 3; Genotyping the sample set whose size was determined by a power analysis (n = 576 appropriate for the initial screening panel; 4 Inference of local ancestry for each individual and identification of regions with increased AA ancestry using two different ancestry inference statistical approaches; 5 Enrichment of the initial screening panel; 6 Power analysis of the enriched panel 7 Genotyping of additional samples. 8 Re-analysis of the genotyping results to identify a genetic risk locus. Results The initial screening phase yielded a significant peak using the ADMIXMAP ancestry inference program applying case only statistics. Subgroup analysis of 299 ESKD patients with no history of diabetes yielded peaks using both the ANCESTRYMAP and ADMIXMAP ancestry inference programs. The significant peak was found on chromosome 22. Genotyping of additional ancestry informative markers on chromosome 22 that took into account linkage disequilibrium in the ancestral populations, and the addition of samples increased the statistical significance of the finding. Conclusions A multi-step admixture mapping analysis of AA ESKD patients replicated the finding of a candidate risk locus on chromosome 22, contributing to the heightened susceptibility of African Americans to develop non

  1. Behavioral immune system and ingroup derogation: the effects of infectious diseases on ingroup derogation attitudes.

    Directory of Open Access Journals (Sweden)

    Qi Wu

    Full Text Available From evolutionary reasoning, we derived a novel hypothesis that ingroup derogation is an evolved response of behavioral immune system which follows the smoke detector principle and the functional flexibility principle. This hypothesis was tested and supported across three experiments. In Experiment 1, participants' group membership was manipulated by using a minimal group paradigm. The results indicated that mere social categorization alone - a heuristic cue that implies the differentiation between "us" and "them" - was sufficient to elicit ingroup derogation among Chinese participants, and, such an intergroup bias was positively associated with the perceived vulnerability to diseases, which was also more consistently associated with ingroup attitudes. Experiment 2 extended and partially replicated Experiment 1 by showing that when there were cues of diseases in the immediate physical environment, Chinese participants exaggerated their attitudes of ingroup derogation. The results also showed that this effect was mainly driven by outgroup attraction. Experiment 3 changed the method of disease manipulation, and found that Chinese participants responded more strongly to disease cues originating from ingroup members and that they endorsed more ingroup derogation attitudes even when the ingroup and outgroup members were both displaying cues of diseases. Taken together, these results reveal the previously unexplored effects of infectious diseases on ingroup derogation attitudes, and suggest an interesting linkage between the evolved behavioral immune system and the ingroup derogation.

  2. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  3. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Schwarz, E.

    2008-01-01

    AIM: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development......, the data of calculated daily macro- and micronutrient intake do not suggest any explicit influence of gender-specific nutrition in the development of ALD....

  4. Transcriptional Innate Immune Response of the Developing Chicken Embryo to Newcastle Disease Virus Infection

    Science.gov (United States)

    Schilling, Megan A.; Katani, Robab; Memari, Sahar; Cavanaugh, Meredith; Buza, Joram; Radzio-Basu, Jessica; Mpenda, Fulgence N.; Deist, Melissa S.; Lamont, Susan J.; Kapur, Vivek

    2018-01-01

    Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust. The expression of CCL5, Mx1, and TLR3 in lung tissues of NDV challenged chicken embryos from the outbred Kuroiler and Tanzanian local ecotype lines showed that their expression was several orders of magnitude higher in the Kuroiler than in the local ecotypes. Next, the expression patterns of three additional innate-immunity related genes, IL-8, IRF-1, and STAT1, were examined in the highly congenic Fayoumi (M5.1 and M15.2) and Leghorn (Ghs6 and Ghs13) sublines that differ only at the microchromosome bearing the major histocompatibility locus. The results show that the Ghs13 Leghorn subline had a consistently higher expression of all genes except IL-8 and expression seemed to be subline-dependent rather than breed-dependent, suggesting that the innate immune response of chicken embryos to NDV infection may be genetically controlled by the MHC-locus. Taken together, the results suggest that the chicken embryo may represent a promising model to studying the patterns and sources of variation of the avian innate immune response to infection with NDV and related pathogens. PMID:29535762

  5. Clinical use of enteral immune nutrition in patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Zhi-cheng ZHANG

    2015-06-01

    Full Text Available Objective To investigate the use of enteral immune nutrition preparation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD, regard its efficacy in improving nutritional status, and its influence on immunity and the status of acute inflammatory reaction of the patients. Methods Sixty-two AECOPD patients requiring mechanical ventilation in ICU of our hospital were randomly divided into two groups: immune nutrition group [study group, n=32, receiving Ruineng (a product of Huarui Pharmaceutical Ltd., which contained essential fatty acids, Omega-3 fatty acids, and energy 1.3 kcal/ml] and conventional nutrition group (control group, n=30, receiving the hospital self-made homogenized diet with 1.2 kal/ml. Patients in the two groups took enteral nutrition of equal calorie, and it was given by nasointestinal tube. On the day of admission and the 14th and 18th after admission, venous blood was obtained for the determination of serum albumin, prealbumin, transferrin, C reactive protein (CRP, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6. At the same time upper arm muscle circumference (MAMC was measured at the bed side. The 14-day off-respirator rate and mechanical ventilation time within 28 days were compared between the two groups. Results The 14-day off-respirator rate was higher in study group than in control group (P0.05. Conclusions Compared with homogenized diet, immune enteral nutrition could better improve the nutritional status and immune function, lower the acute inflammatory response level, increase the success rate of early off-respirator in AECOPD patients, therefore, enteral immune nutrition preparation is a better nutrition support solution for AECOPD. DOI: 10.11855/j.issn.0577-7402.2015.05.17

  6. Transcriptional Innate Immune Response of the Developing Chicken Embryo to Newcastle Disease Virus Infection

    Directory of Open Access Journals (Sweden)

    Megan A. Schilling

    2018-02-01

    Full Text Available Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust. The expression of CCL5, Mx1, and TLR3 in lung tissues of NDV challenged chicken embryos from the outbred Kuroiler and Tanzanian local ecotype lines showed that their expression was several orders of magnitude higher in the Kuroiler than in the local ecotypes. Next, the expression patterns of three additional innate-immunity related genes, IL-8, IRF-1, and STAT1, were examined in the highly congenic Fayoumi (M5.1 and M15.2 and Leghorn (Ghs6 and Ghs13 sublines that differ only at the microchromosome bearing the major histocompatibility locus. The results show that the Ghs13 Leghorn subline had a consistently higher expression of all genes except IL-8 and expression seemed to be subline-dependent rather than breed-dependent, suggesting that the innate immune response of chicken embryos to NDV infection may be genetically controlled by the MHC-locus. Taken together, the results suggest that the chicken embryo may represent a promising model to studying the patterns and sources of variation of the avian innate immune response to infection with NDV and related pathogens.

  7. Short communication: Association of disease incidence and adaptive immune response in Holstein dairy cows.

    Science.gov (United States)

    Thompson-Crispi, K A; Hine, B; Quinton, M; Miglior, F; Mallard, B A

    2012-07-01

    The objective of this study was to use previously calculated estimated breeding values for cell- (CMIR) and antibody-mediated immune responses (AMIR) to determine associations between immune response (IR) and economically important diseases of dairy cattle. In total, 699 Holsteins were classified as high, average, or low for CMIR, AMIR, and overall IR (combined CMIR and AMIR), and associations with mastitis, metritis, ketosis, displaced abomasums, and retained fetal membranes were determined. The incidence of mastitis was higher among average cows as compared with cows classified as high AMIR [odds ratio (OR)=2.5], high CMIR (OR=1.8), or high IR (OR=1.8). Low-CMIR cows had a higher incidence of metritis (OR=11.3) and low-IR cows had a higher incidence of displaced abomasum (OR=4.1) and retained fetal membrane (OR=2.8) than did average responders. Results of this study show that cows classified as high immune responders have lower occurrence of disease, suggesting that breeding cattle for enhanced IR may be a feasible approach to decrease the incidence of infectious and metabolic diseases in the dairy industry. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

    Science.gov (United States)

    Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash; Kothary, Rashmi

    2017-02-15

    Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. © The Author 2017. Published by Oxford University Press.

  9. Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

    Science.gov (United States)

    Chotirmall, Sanjay H.; Al-Alawi, Mazen; Logan, P. Mark; Greene, Catherine M.; McElvaney, Noel G.

    2013-01-01

    Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit. PMID:23971044

  10. Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Sanjay H. Chotirmall

    2013-01-01

    Full Text Available Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

  11. GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases

    Institute of Scientific and Technical Information of China (English)

    Yin Yao Shugart; Ying Wang; Wei-Hua Jia; Yi-Xin Zeng

    2011-01-01

    Increasing evidence suggests that multiple genes in the human leukocyte antigen (HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

  12. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  13. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    Full Text Available Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS, providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  14. Epizootic to enzootic transition of a fungal disease in tropical Andean frogs: Are surviving species still susceptible?

    Directory of Open Access Journals (Sweden)

    Alessandro Catenazzi

    Full Text Available The fungal pathogen Batrachochytrium dendrobatidis (Bd, which causes the disease chytridiomycosis, has been linked to catastrophic amphibian declines throughout the world. Amphibians differ in their vulnerability to chytridiomycosis; some species experience epizootics followed by collapse while others exhibit stable host/pathogen dynamics where most amphibian hosts survive in the presence of Bd (e.g., in the enzootic state. Little is known about the factors that drive the transition between the two disease states within a community, or whether populations of species that survived the initial epizootic are stable, yet this information is essential for conservation and theory. Our study focuses on a diverse Peruvian amphibian community that experienced a Bd-caused collapse. We explore host/Bd dynamics of eight surviving species a decade after the mass extinction by using population level disease metrics and Bd-susceptibility trials. We found that three of the eight species continue to be susceptible to Bd, and that their populations are declining. Only one species is growing in numbers and it was non-susceptible in our trials. Our study suggests that some species remain vulnerable to Bd and exhibit ongoing population declines in enzootic systems where Bd-host dynamics are assumed to be stable.

  15. Association of immune response to endothelial cell growth factor with early disseminated and late manifestations of Lyme disease but not posttreatment Lyme disease syndrome.

    Science.gov (United States)

    Tang, Kevin S; Klempner, Mark S; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2015-12-01

    Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Tuberculoid leprosy and cytomegalovirus retinitis as immune restoration disease in a patient with AIDS.

    Science.gov (United States)

    Kumar, Shishir; Ghosh, Manab Kumar; Sarkar, Somenath; Mallik, Sudeshna; Biswas, Pradyot Narayan; Saha, Bibhuti

    2012-02-01

    Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Fatigue in patients with inflammatory bowel disease is associated with distinct differences in immune parameters

    Directory of Open Access Journals (Sweden)

    Vogelaar L

    2017-05-01

    Full Text Available Lauran Vogelaar, 1,* Colin de Haar,2,* Bas RJ Aerts,1 Maikel P Peppelenbosch,1 Reinier Timman,3 Bettina E Hanssen,1 C Janneke van der Woude1 1Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, 2Applied Tumor Immunology, Laboratory of Translational Immunology, UMC Utrecht, Utrecht, 3Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus MC, Rotterdam, the Netherlands *These authors contributed equally to this work Background: Although it is well recognized that fatigue is an important problem in many of the quiescent inflammatory bowel disease (IBD patients, it is unknown whether the immune status is different in fatigued versus non-fatigued patients. In this study, we contrasted various characteristics of the immune system in fatigued against non-fatigued patients with IBD in clinical remission.Patients and methods: Patients with IBD in clinical remission were phenotyped according to the Montreal classification, and the checklist individual strength-fatigue (CIS-fatigue was used to assess fatigue (CIS-fatigue ≥ 35. Flow cytometry on peripheral blood samples was used to investigate differences in leukocyte subsets. The expression of various cytokines was determined in stimulated whole blood and serum samples using enzyme-linked immunosorbent assay. Differences between fatigued and non-fatigued patients with IBD were assessed.Results: In total, 55 patients were included in the fatigue group (FG and 29 patients in the non-fatigue group (NFG. No differences in demographic and clinical characteristics were observed between the groups. Flow cytometry data showed a significantly lower percentage of monocytes (p = 0.011 and a higher percentage of memory T-cells (p = 0.005 and neutrophils (p = 0.033 in the FG compared with the NFG. Whole blood stimulation showed increased TNF-α (p = 0.022 and IFN-γ (p = 0.047 in the FG. The median serum level was significantly higher for IL-12 (p < 0.001 and IL-10 (p

  18. Genetic analysis of infectious diseases: Estimating gene effects for susceptibility and infectivity

    NARCIS (Netherlands)

    Anche, M.T.; Bijma, P.; Jong, de M.C.M.

    2015-01-01

    Background: Genetic selection of livestock against infectious diseases can complement existing interventions to control infectious diseases. Most genetic approaches that aim at reducing disease prevalence assume that individual disease status (infected/not-infected) is solely a function of its

  19. Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility.

    Science.gov (United States)

    Zhou, Tian-Biao; Jiang, Zong-Pei; Huang, Miao-Fang

    2015-02-01

    Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR = 1.12, 95% CI: 0.88-1.44, p = 0.36; BB genotype: OR = 1.15, 95% CI: 0.81-1.62, p = 0.43; bb genotype: OR = 0.86, 95% CI: 0.61-1.20, p = 0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.

  20. Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility

    NARCIS (Netherlands)

    Chang, Chia-Jung; Kuo, Ho-Chang; Chang, Jeng-Sheng; Lee, Jong-Keuk; Tsai, Fuu-Jen; Khor, Chiea Chuen; Chang, Li-Ching; Chen, Shih-Ping; Ko, Tai-Ming; Liu, Yi-Min; Chen, Ying-Ju; Hong, Young Mi; Jang, Gi Young; Hibberd, Martin L.; Kuijpers, Taco; Burgner, David; Levin, Michael; Burns, Jane C.; Davila, Sonia; Chen, Yuan-Tsong; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lee, Yi-Ching; Liang, Chi-Di; Hwang, Kao-Pin; Chang, Luan-Yin; Huang, Li-Min; Chen, Ming-Ren; Chi, Hsin; Huang, Fu-Yuan; Chiu, Nan-Chang; Lee, Meng-Luen; Huang, Yhu-Chering; Hwang, Betau; Lee, Pi-Chang; Yoo, Jeong-Jin; Park, In-Sook; Hong, Soo-Jong; Kim, Kwi-Joo; Kim, Jae-Jung; Sohn, Saejung; Young Jang, Gi; Ha, Kee-Soo; Nam, Hyo-Kyoung; Byeon, Jung-Hye; Yun, Sin Weon; Han, Myung Ki; Kuipers, Irene M.; Ottenkamp, Jaap J.; Biezeveld, Maarten

    2013-01-01

    The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in

  1. The effect of nitrogen fertilization and irradiation on barley susceptibility to net blotch disease

    International Nuclear Information System (INIS)

    Arabi, M.I.E.; Al-safadi, B.; Charbaji, T.

    2000-11-01

    Isolates of Drechslera teres f. sp. teres that cause net blotch symptoms on barley were collected from fields in different regions of Syria. there virulence spectra were determined using 11 barley cultivars. Cultivars exhibited a continuos range of response from very susceptible to moderately resistant. Isolate Raqa 13 had the highest mean virulence, then Halap 2, whereas ICARDA 3 was the lowest virulent. The effect of three concentrations (1000, 1500, 2000 ppm) of nitrogen (Urea 45%) fertilizer, and two doses of gamma ray (10 and 20 Gy), on susceptibility to infection by Drechslera teres were studied. Two barley cultivars (Thibaut and Furia) were used in this study. Results showed that 1000 ppm (N) and 15 Gy dose treatment had a positive effect on decreasing the susceptibility. (author)

  2. Antagonism between phytohormone signalling underlies the variation in disease susceptibility of tomato plants under elevated CO2

    Science.gov (United States)

    Zhang, Shuai; Li, Xin; Sun, Zenghui; Shao, Shujun; Hu, Lingfei; Ye, Meng; Zhou, Yanhong; Xia, Xiaojian; Yu, Jingquan; Shi, Kai

    2015-01-01

    Increasing CO2 concentrations ([CO2]) have the potential to disrupt plant–pathogen interactions in natural and agricultural ecosystems, but the research in this area has often produced conflicting results. Variations in phytohormone salicylic acid (SA) and jasmonic acid (JA) signalling could be associated with variations in the responses of pathogens to plants grown under elevated [CO2]. In this study, interactions between tomato plants and three pathogens with different infection strategies were compared. Elevated [CO2] generally favoured SA biosynthesis and signalling but repressed the JA pathway. The exposure of plants to elevated [CO2] revealed a lower incidence and severity of disease caused by tobacco mosaic virus (TMV) and by Pseudomonas syringae, whereas plant susceptibility to necrotrophic Botrytis cinerea increased. The elevated [CO2]-induced and basal resistance to TMV and P. syringae were completely abolished in plants in which the SA signalling pathway nonexpressor of pathogenesis-related genes 1 (NPR1) had been silenced or in transgenic plants defective in SA biosynthesis. In contrast, under both ambient and elevated [CO2], the susceptibility to B. cinerea highly increased in plants in which the JA signalling pathway proteinase inhibitors (PI) gene had been silenced or in a mutant affected in JA biosynthesis. However, plants affected in SA signalling remained less susceptible to this disease. These findings highlight the modulated antagonistic relationship between SA and JA that contributes to the variation in disease susceptibility under elevated [CO2]. This information will be critical for investigating how elevated CO2 may affect plant defence and the dynamics between plants and pathogens in both agricultural and natural ecosystems. PMID:25657213

  3. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  4. Altered Immune Regulation in Type 1 Diabetes

    Science.gov (United States)

    Zóka, András; Műzes, Györgyi; Somogyi, Anikó; Varga, Tímea; Szémán, Barbara; Al-Aissa, Zahra; Hadarits, Orsolya; Firneisz, Gábor

    2013-01-01

    Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development. PMID:24285974

  5. Altered Immune Regulation in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    András Zóka

    2013-01-01

    Full Text Available Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.

  6. The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases.

    Science.gov (United States)

    Yin, Jinghua; Zhang, Jian; Lu, Qianjin

    2017-07-01

    Basic leucine zipper transcription factor E4BP4 (also known as NFIL3) has been implicated in the molecular and cellular mechanisms of functions and activities in mammals. The interactions between E4BP4 and major regulators of cellular processes have triggered significant interest in the roles of E4BP4 in the pathogenesis of certain chronic diseases. Indeed, novel discoveries have been emerging to illustrate the involvement of E4BP4 in multiple disorders. It is recognized that E4BP4 is extensively involved in some immune-mediated diseases, but the mechanisms of E4BP4 involvement in these complex diseases remain poorly defined. Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies. Copyright © 2017. Published by Elsevier Inc.

  7. Anatomical localization of commensal bacteria in immune cell homeostasis and disease.

    Science.gov (United States)

    Fung, Thomas C; Artis, David; Sonnenberg, Gregory F

    2014-07-01

    The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in the intestine, including the surface of intestinal epithelial cells (IECs) and the interior of gut-associated lymphoid tissues. These distinct tissue localization patterns permit unique interactions with the mammalian immune system and collectively influence intestinal immune cell homeostasis. Conversely, dysregulated localization of commensal bacteria can lead to inappropriate activation of the immune system and is associated with numerous chronic infectious, inflammatory, and metabolic diseases. Therefore, regulatory mechanisms that control proper anatomical containment of commensal bacteria are essential to maintain tissue homeostasis and limit pathology. In this review, we propose that commensal bacteria associated with the mammalian GI tract can be anatomically defined as (i) luminal, (ii) epithelial-associated, or (iii) lymphoid tissue-resident, and we discuss the role and regulation of these microbial populations in health and disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases.

    Science.gov (United States)

    García Bueno, B; Caso, J R; Madrigal, J L M; Leza, J C

    2016-05-01

    The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

    Science.gov (United States)

    Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

    2015-01-01

    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

  10. Population growth changes targets for immunization.

    Science.gov (United States)

    Tuljapurkar, S; John, A M

    1995-01-01

    The faster the rate of population growth in developing countries, the less likely it is that current protocols for immunization against measles, rubella, and mumps will eradicate these childhood diseases. Standard protocols (timing, percentage of children to be immunized) do not take into account the rapid rates of population growth in developing countries (3.0% per year on average in sub-Saharan Africa and 2.0% in the rest of Africa, in Latin America, and in Asia, excluding China). Most public health planning models in this area were created based on static infant populations. The World Health Organization advises vaccinating at least 85% of children aged 6 to 9 months, a 3-month immunization window during which maternal antibodies are low (so the vaccination takes) and herd immunity is high (the probability that a child will encounter the disease is low because most children have been immunized). In practice, the immunization window in developing countries is 1 year or more. More susceptible children are present than assumed by the models. A larger number of susceptible babies are added each year during rapid population growth. As the age range for immunization widens, a higher percentage of children must be vaccinated to eradicate disease (chart). The proportion of each birth cohort that must be immunized rises as the population growth rate increases. At zero population growth, 94% must be vaccinated; at population growth rates greater than 3%, 98% must be vaccinated.

  11. Terpene Profile, Leaf Anatomy, and Enzyme Activity of Resistant and Susceptible Cocoa Clonesto Vascular Streak Dieback Disease

    Directory of Open Access Journals (Sweden)

    Adi Prawoto

    2014-10-01

    Full Text Available Vascular-streak dieback (VSD, Oncobasidium theobromae is the most prevalent disease of Theobroma cacao L. in Indonesia. This study aims to analyze resistance mechanism to VSD based on terpene profile, leaf anatomy, chitinase, and peroxidase study. Resistant clones of Sulawesi 1 and Sca 6 and susceptible clones of ICS 60 and TSH 858 were used for terpene profile, leaf anatomy analysis, chitinase, peroxides, polyphenol, lignin, and cellulose analysis. Those clones and KEE 2, KKM 22 and ICS 13 were used for peroxides analysis. For trichome study, the resistant clones of Sulawesi 1, Sca 6, KEE 2, and KKM 22, and susceptible clones of ICS 60 and TSH 858 were used. GCMS analysis showed that chromatogram pattern of resistant and susceptible groups were quite similar, but resistant clones contained 22% more components than the susceptible ones. Resistant clones contained groups of pinene, decane, myrcene, and octadecanoic acid, while those substances on usceptible clones were absent. Trichome was thicker on younger leaf, and its density on the basal was higher than that on the middle and tip leaf parts. Trichome density of resistant clone was not always thicker than that of susceptible ones. On resistant clones, stomatal density was lower and width of stomate pits was narrower, while thickness of epidermis layer and pallisade parenchym were higher. Polyphenol content of resistant clones were higher but lignin and cellulose of both groups were similar. Chitinase activity which has a role in hydrolysis of mycelia cell wall was higher on the resistant clones, but peroxides which has a role in polymeration of lignin biosynthesis was similar between both groups. It is concluded that groups of terpene pinene, decane, myrcene, and octadecanoic acid, thickness of leaf epidermis, density and width of stomata pit, and chitinase activity plays important role in cocoa resistance to VSD. Key words: Theobroma cacaoL., clone, vascular-streak dieback, resistance, leaf

  12. Regulation of the Immune Response to α-Gal and Vector-borne Diseases.

    Science.gov (United States)

    Cabezas-Cruz, Alejandro; Mateos-Hernández, Lourdes; Pérez-Cruz, Magdiel; Valdés, James J; Mera, Isabel G Fernández de; Villar, Margarita; de la Fuente, José

    2015-10-01

    Vector-borne diseases (VBD) challenge our understanding of emerging diseases. Recently, arthropod vectors have been involved in emerging anaphylactic diseases. In particular, the immunoglobulin E (IgE) antibody response to the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-gal) following a tick bite was associated with allergies to red meat, cetuximab, and gelatin. By contrast, an anti-α-gal IgM antibody response was shown to protect against mosquito-borne malaria. Herein, we highlight the interplay between the gut microbiota, vectors, transmitted pathogens, and the regulation of the immune response as a model to understand the protective or allergic effect of α-gal. Establishing the source of α-gal in arthropod vectors and the immune response to vector bites and transmitted pathogens will be essential for diagnosing, treating, and ultimately preventing these emerging anaphylactic and other vector-borne diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    DEFF Research Database (Denmark)

    Sud, Amit; Thomsen, Hauke; Law, Philip J.

    2017-01-01

    Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 co...

  14. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    NARCIS (Netherlands)

    Sud, A. (Amit); Thomsen, H. (Hauke); Law, P.J. (Philip J.); A. Försti (Asta); Filho, M.I.D.S. (Miguel Inacio Da Silva); Holroyd, A. (Amy); P. Broderick (Peter); Orlando, G. (Giulia); Lenive, O. (Oleg); Wright, L. (Lauren); R. Cooke (Rosie); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); J. Peto (Julian); F. Canzian (Federico); Eeles, R. (Rosalind); Z. Kote-Jarai; K.R. Muir (K.); Pashayan, N. (Nora); B.E. Henderson (Brian); C.A. Haiman (Christopher); S. Benlloch (Sara); F.R. Schumacher (Fredrick R); Olama, A.A.A. (Ali Amin Al); S.I. Berndt (Sonja); G. Conti (Giario); F. Wiklund (Fredrik); S.J. Chanock (Stephen); Stevens, V.L. (Victoria L.); C.M. Tangen (Catherine M.); Batra, J. (Jyotsna); Clements, J. (Judith); H. Grönberg (Henrik); Schleutker, J. (Johanna); D. Albanes (Demetrius); Weinstein, S. (Stephanie); K. Wolk (Kerstin); West, C. (Catharine); Mucci, L. (Lorelei); Cancel-Tassin, G. (Géraldine); Koutros, S. (Stella); Sorensen, K.D. (Karina Dalsgaard); L. Maehle; D. Neal (David); S.P.L. Travis (Simon); Hamilton, R.J. (Robert J.); S.A. Ingles (Sue); B.S. Rosenstein (Barry S.); Lu, Y.-J. (Yong-Jie); Giles, G.G. (Graham G.); A. Kibel (Adam); Vega, A. (Ana); M. Kogevinas (Manolis); Penney, K.L. (Kathryn L.); Park, J.Y. (Jong Y.); Stanford, J.L. (Janet L.); C. Cybulski (Cezary); B.G. Nordestgaard (Børge); Brenner, H. (Hermann); Maier, C. (Christiane); Kim, J. (Jeri); E.M. John (Esther); P.J. Teixeira; Neuhausen, S.L. (Susan L.); De Ruyck, K. (Kim); Razack, A. (Azad); Newcomb, L.F. (Lisa F.); Lessel, D. (Davor); Kaneva, R. (Radka); N. Usmani (Nawaid); F. Claessens; Townsend, P.A. (Paul A.); Dominguez, M.G. (Manuela Gago); Roobol, M.J. (Monique J.); F. Menegaux (Florence); P. Hoffmann (Per); M.M. Nöthen (Markus); K.-H. JöCkel (Karl-Heinz); Strandmann, E.P.V. (Elke Pogge Von); Lightfoot, T. (Tracy); Kane, E. (Eleanor); Roman, E. (Eve); Lake, A. (Annette); Montgomery, D. (Dorothy); Jarrett, R.F. (Ruth F.); A.J. Swerdlow (Anthony ); A. Engert (Andreas); N. Orr (Nick); K. Hemminki (Kari); Houlston, R.S. (Richard S.)

    2017-01-01

    textabstractSeveral susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and

  15. Innate immune signalling at the intestinal epithelium in homeostasis and disease

    Science.gov (United States)

    Pott, Johanna; Hornef, Mathias

    2012-01-01

    The intestinal epithelium—which constitutes the interface between the enteric microbiota and host tissues—actively contributes to the maintenance of mucosal homeostasis and defends against pathogenic microbes. The recognition of conserved microbial products by cytosolic or transmembrane pattern recognition receptors in epithelial cells initiates signal transduction and influences effector cell function. However, the signalling pathways, effector molecules and regulatory mechanisms involved are not yet fully understood, and the functional outcome is poorly defined. This review analyses the complex and dynamic role of intestinal epithelial innate immune recognition and signalling, on the basis of results in intestinal epithelial cell-specific transgene or gene-deficient animals. This approach identifies specific epithelial cell functions within the diverse cellular composition of the mucosal tissue, in the presence of the complex and dynamic gut microbiota. These insights have thus provided a more comprehensive understanding of the role of the intestinal epithelium in innate immunity during homeostasis and disease. PMID:22801555

  16. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  17. Variable activation of immune response by quinoa (Chenopodium quinoa Willd.) prolamins in celiac disease.

    Science.gov (United States)

    Zevallos, Victor F; Ellis, H Julia; Suligoj, Tanja; Herencia, L Irene; Ciclitira, Paul J

    2012-08-01

    Celiac disease is an enteropathy triggered by dietary gluten found in wheat, barley, and rye. The current treatment is a strict gluten-free diet. Quinoa is a highly nutritive plant from the Andes, with low concentrations of prolamins, that has been recommended as part of a gluten-free diet; however, few experimental data support this recommendation. We aimed to determine the amount of celiac-toxic prolamin epitopes in quinoa cultivars from different regions of the Andes and the ability of these epitopes to activate immune responses in patients with celiac disease. The concentration of celiac-toxic epitopes was measured by using murine monoclonal antibodies against gliadin and high-molecular-weight glutenin subunits. Immune response was assessed by proliferation assays of celiac small intestinal T cells/interferon-γ (IFN-γ) and production of IFN-γ/IL-15 after organ culture of celiac duodenal biopsy samples. Fifteen quinoa cultivars were tested: 4 cultivars had quantifiable concentrations of celiac-toxic epitopes, but they were below the maximum permitted for a gluten-free food. Cultivars Ayacuchana and Pasankalla stimulated T cell lines at levels similar to those for gliadin and caused secretion of cytokines from cultured biopsy samples at levels comparable with those for gliadin. Most quinoa cultivars do not possess quantifiable amounts of celiac-toxic epitopes. However, 2 cultivars had celiac-toxic epitopes that could activate the adaptive and innate immune responses in some patients with celiac disease. These findings require further investigation in the form of in vivo studies, because quinoa is an important source of nutrients for patients with celiac disease.

  18. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2016-11-01

    Full Text Available Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD. Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10 chemokine ligands [ITAC (CXCL11 and Mig (CXCL9] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1, and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of

  19. Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients.

    Directory of Open Access Journals (Sweden)

    Cathy J Jensen

    Full Text Available Recent association studies in multiple sclerosis (MS have identified and replicated several single nucleotide polymorphism (SNP susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13-14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.

  20. Diagnosis of acute radiation disease by Enzyme Immune-Assay (EIA)

    International Nuclear Information System (INIS)

    Popov, D.; Maliev, V.; Jones, J.; Gonta, S.; Prasad, K.; Rachal, C.

    2006-01-01

    Diagnosis of the acute radiation disease by the method of immune enzyme assay is a simple and efficient tool of evaluating and biological dosimetry and forecasting of development of the acute radiation defeats as at group of population so at individuals locating in the zone polluted by the radiation. We use as biological markers the group of essential radiotoxins - high molecular mass glycoprotein ( molecular mass - 200 - 250 kDa ) - radiation antigens (S.D.R. - specific radiation determinant ) accumulated in the lymphoid system, with epitopes specific to each form of radiation syndrome, after animals have been irradiated in doses inducing the development of the cerebral (1), toxic ( 2), gastrointestinal ( 3 ) and typical ( 4 ) forms of acute radiation sickness. These two phenomena allowed us to develop a technologies for diagnosis, prophylaxis and therapy of radiation disease - enzyme immune assay ( EIA ), anti radiation vaccine, anti radiation serum, method of immune - lymph - plasma-sorption. The important first step in effectiveness of therapy is an accurate assessment of severity of disease in early period after irradiation. The ideal markers for early and accurate assessment is high weight glycoprotein with specifics radiation induced features (S.D.R.) mentioned above. This biology active substance isolated from lymph can induct the symptoms of radiation syndrome without previously radiation when it is administrated intra-muscularly or intravenously to healthy animals. Enzyme immune assay (EIA) allowed researchers to indicate the significant levels of different forms of S.D.R. in peripheral blood of animals in first 24 hours after radiation. Indication of high level of S.D.R. -1 allowed to forecast a fast development of cerebral form of acute radiation disease. Determination of high levels of S.D.R.-2, S.D.R.-3 and S.D.R.-4 in peripheral blood allowed to recognize early periods of toxic, gastrointestinal and typical forms of acute radiation sickness

  1. Diagnosis of acute radiation disease by Enzyme Immune-Assay (EIA)

    Energy Technology Data Exchange (ETDEWEB)

    Popov, D.; Maliev, V. [Russian Academy of Science, Vladicaukas (Russian Federation); Jones, J.; Gonta, S. [NASA -Johnson Spa ce Center, Houston (United States); Prasad, K. [Antioxidant Research Institute, Premier Micrinutrient corporation, Novato (United States); Rachal, C. [Univercity Space Research Assotiation, Colorado (United States)

    2006-07-01

    Diagnosis of the acute radiation disease by the method of immune enzyme assay is a simple and efficient tool of evaluating and biological dosimetry and forecasting of development of the acute radiation defeats as at group of population so at individuals locating in the zone polluted by the radiation. We use as biological markers the group of essential radiotoxins - high molecular mass glycoprotein ( molecular mass - 200 - 250 kDa ) - radiation antigens (S.D.R. - specific radiation determinant ) accumulated in the lymphoid system, with epitopes specific to each form of radiation syndrome, after animals have been irradiated in doses inducing the development of the cerebral (1), toxic ( 2), gastrointestinal ( 3 ) and typical ( 4 ) forms of acute radiation sickness. These two phenomena allowed us to develop a technologies for diagnosis, prophylaxis and therapy of radiation disease - enzyme immune assay ( EIA ), anti radiation vaccine, anti radiation serum, method of immune - lymph - plasma-sorption. The important first step in effectiveness of therapy is an accurate assessment of severity of disease in early period after irradiation. The ideal markers for early and accurate assessment is high weight glycoprotein with specifics radiation induced features (S.D.R.) mentioned above. This biology active substance isolated from lymph can induct the symptoms of radiation syndrome without previously radiation when it is administrated intra-muscularly or intravenously to healthy animals. Enzyme immune assay (EIA) allowed researchers to indicate the significant levels of different forms of S.D.R. in peripheral blood of animals in first 24 hours after radiation. Indication of high level of S.D.R. -1 allowed to forecast a fast development of cerebral form of acute radiation disease. Determination of high levels of S.D.R.-2, S.D.R.-3 and S.D.R.-4 in peripheral blood allowed to recognize early periods of toxic, gastrointestinal and typical forms of acute radiation sickness

  2. Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease

    NARCIS (Netherlands)

    Zoodsma, M; Nolte, IM; Schipper, M; Oosterom, E; Van der Steege, G; De Vries, EGE; Te Meerman, GJ; Van der Zee, AGJ

    2005-01-01

    Infection with oncogenic types of human papillomavirus (HPV) is the main causal factor of cervical cancer and its precursor lesion (cervical intraepithelial neoplasia [CIN]). Cellular immunity may be critical in the elimination of HPV-harboring cells. Interleukin-10, a T-helper type 2 cytokine, has

  3. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

    Science.gov (United States)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

    2018-03-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

  4. Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

    Directory of Open Access Journals (Sweden)

    Juan Marcos Mucci

    2015-01-01

    Full Text Available Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

  5. Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease

    Science.gov (United States)

    Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina; Pierce, Susan K.

    2014-01-01

    Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease. PMID:24655294

  6. Maternal Infectious Diseases, Antimicrobial Therapy or Immunizations: Very few Contraindications to Breastfeeding

    Directory of Open Access Journals (Sweden)

    Noni E Macdonald

    2006-01-01

    Full Text Available The Canadian Paediatric Society recommends exclusive breastfeeding as the optimal method of infant feeding for the first six months of life for healthy, term infants (1. There are many benefits associated with breastfeeding, including nutritional, immunological, psychological, developmental, environmental, social, economic and health (eg, decrease in infectious diseases (2-4. To promote, protect and support breastfeeding, every effort must be made to minimize contraindications to breastfeeding, particularly unnecessary ones. The present article summarizes the maternal infectious diseases in which continuing breastfeeding is recommended, the very few infectious diseases in which it is not recommended, the rare instances in which maternal antimicrobial therapy indicates a caution for breastfeeding, and the continuation of breastfeeding when a mother or her infant is receiving a routine recommended immunization.

  7. Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Nath KD

    2013-12-01

    Full Text Available Karthik D Nath,1,2 Julie G Burel,1 Viswanathan Shankar,3 Antonia L Pritchard,1 Michelle Towers,2 David Looke,1,2 Janet M Davies,1 John W Upham1,2 1The University of Queensland (School of Medicine, Brisbane, QLD, Australia; 2Princess Alexandra Hospital, Brisbane, QLD, Australia; 3Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA Background and objective: Individuals with chronic obstructive pulmonary disease (COPD are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine. Methods: In this observational study, 34 subjects (20 COPD, 14 healthy received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline and the fold increase in antibody titer after vaccination. Results: Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036. Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity. Conclusion: The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with

  8. Local and systemic humoral immune response in farmed Atlantic salmon (Salmo salar L.) under a natural amoebic gill disease outbreak.

    Science.gov (United States)

    Marcos-López, Mar; Espinosa Ruiz, Cristóbal; Rodger, Hamish D; O'Connor, Ian; MacCarthy, Eugene; Esteban, M Ángeles

    2017-07-01

    Amoebic gill disease (AGD), caused by the protozoan parasite Neoparamoeba perurans, is one of the most significant infectious diseases for Atlantic salmon (Salmo salar L.) mariculture. The present study investigated the humoral immune response (both local in gill mucus and systemic in serum) of farmed Atlantic salmon naturally infected with N. perurans in commercial sea pens, at two different stages of the disease and after freshwater treatment. Parameters analysed included activity of immune related enzymes (i.e. lysozyme, peroxidase, protease, anti-protease, esterase, alkaline phosphatase), IgM levels, and the terminal carbohydrate profile in the gill mucus. Overall, greater variations between groups were noted in the immune parameters determined in gill mucus than the equivalent in the serum. In gill mucus, IgM levels and peroxidase, lysozyme, esterase and protease activities were decreased in fish showing longer exposure time to the infection and higher disease severity, then showed a sequential increase after treatment. Results obtained highlight the capacity of gills to elicit a local response to the infection, indicate an impaired immune response at the later stages of the disease, and show partial reestablishment of the host immune status after freshwater treatment. In addition to providing data on the humoral response to AGD, this study increases knowledge on gill mucosal humoral immunity, since some of the parameters were analysed for the first time in gill mucus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Complement modulation of T cell immune responses during homeostasis and disease.

    Science.gov (United States)

    Clarke, Elizabeth V; Tenner, Andrea J

    2014-11-01

    The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders. © 2014 Society for Leukocyte Biology.

  10. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides

    Science.gov (United States)

    Jia, Haibo; Halilou, Amadou I.; Hu, Liang; Cai, Wenqian; Liu, Jing; Huang, Bo

    2011-01-01

    Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule. PMID:21969171

  11. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    Science.gov (United States)

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

  12. Cardiovascular Disease Biomarkers Predict Susceptibility or Resistance to Lung Injury in World Trade Center Dust Exposed Firefighters

    Science.gov (United States)

    Weiden, Michael D.; Naveed, Bushra; Kwon, Sophia; Cho, Soo Jung; Comfort, Ashley L.; Prezant, David J.; Rom, William N.; Nolan, Anna

    2013-01-01

    Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome, predicts loss of lung function in World Trade Center Lung Injury (WTC-LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI. This nested case-cohort study used 801 never smoker, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March, 2008. A representative sub-cohort of 124/801 with serum drawn within six months of 9/11 defined CVD biomarker distribution. Post-9/11/01 FEV1 at subspecialty exam defined cases: susceptible WTC-LI cases with FEV1≤77% predicted (66/801) and resistant WTC-LI cases with FEV1≥107% (68/801). All models were adjusted for WTC exposure intensity, BMI at SPE, age at 9/11, and pre-9/11 FEV1. Susceptible WTC-LI cases had higher levels of Apo-AII, CRP, and MIP-4 with significant RRs of 3.85, 3.93, and 0.26 respectively with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher sVCAM and lower MPO with RRs of 2.24, and 2.89 respectively; AUC 0.830. Biomarkers of CVD in serum six-month post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure. PMID:22903969

  13. Lack of association between miR-218 rs11134527 A>G and Kawasaki disease susceptibility.

    Science.gov (United States)

    Pi, Lei; Fu, Lanyan; Xu, Yufen; Che, Di; Deng, Qiulian; Huang, Xijing; Li, Meiai; Zhang, Li; Huang, Ping; Gu, Xiaoqiong

    2018-05-01

    Abstract Kawasaki disease (KD) is a type of disease that includes the development of a fever that lasts at least five days and involves the clinical manifestation of multicellular vasculitis. KD has become one of the most common pediatric cardiovascular diseases. Previous studies have reported that miR-218 rs11134527 A>G is associated with susceptibility to various cancer risks. However, there is a lack of evidence regarding the relationship between this polymorphism and KD risk. This study explored the correlation between the miR-218 rs11134527 A>G polymorphism and the risk of KD. We recruited 532 patients with KD and 623 controls to genotype the miR-218 rs11134527 A>G polymorphism with a TaqMan allelic discrimination assay. Our results illustrated that the miR-218 rs11134527 A>G polymorphism was not associated with KD risk. In an analysis stratified by age, sex, and coronary artery lesions, we found only that the risk of KD was significantly decreased for children older than 5 years (GG vs. AA/AG: adjusted OR=0.26, 95% CI=0.07-0.94, P =0.041). This study demonstrated that the miR-218 rs1113452 A>G polymorphism may have an age-related relationship with KD susceptibility that has not previously been revealed. ©2018 The Author(s).

  14. Using case-control designs for genome-wide screening for associations between genetic markers and disease susceptibility loci.

    Science.gov (United States)

    Yang, Q; Khoury, M J; Atkinson, M; Sun, F; Cheng, R; Flanders, W D

    1999-01-01

    We used a case-control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case-control approach, we constructed a series of 2-by-3 tables for each allele of every marker on all six chromosomes. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated for all alleles of every marker. We selected the one allele for which the estimated OR had the minimum p-value to plot in the graph. Among these selected ORs, we calculated 95% CI for those that had a p-value Mycenaean population, the case-control design identified allele number 1 of marker 24 on chromosome 1 to be associated with a disease susceptibility gene, OR = 2.10 (95% CI 1.66-2.62). Our approach failed to show any other significant association between case-control status and genetic markers. Stratified analysis on the environmental risk factor (E1) provided no further evidence of significant association other than allele 1 of marker 24 on chromosome 1. These data indicate the absence of linkage disequilibrium for markers flanking loci A, B, and C. Finally, we examined the effect of gene x environment (G x E) interaction for the identified allele. Our results provided no evidence of G x E interaction, but suggested that the environmental exposure alone was a risk factor for the disease.

  15. Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.

    Science.gov (United States)

    Chung, Sun Ju; Armasu, Sebastian M; Anderson, Kari J; Biernacka, Joanna M; Lesnick, Timothy G; Rider, David N; Cunningham, Julie M; Ahlskog, J Eric; Frigerio, Roberta; Maraganore, Demetrius M

    2013-06-01

    Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Five pairwise interactions had uncorrected P-values coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. The immunization status of children with chronic neurological disease and serological assessment of vaccine-preventable diseases.

    Science.gov (United States)

    Dinleyici, Meltem; Carman, Kursat Bora; Kilic, Omer; Laciner Gurlevik, Sibel; Yarar, Coskun; Dinleyici, Ener Cagri

    2018-04-06

    The aim of this study was to evaluate the age-appropriate immunization coverage in 366 children with chronic neurological disease (CND), to evaluate the use of vaccines not included in routine program, to evaluate serological tests for vaccine-preventable diseases and to describe the related factors in unvaccinated children. 95.6% of all children with had received age-appropriate vaccinations according to the actual National Immunization Program (NIP) during childhood. 12 children (3.6%) had not received vaccines; only two had true contraindications. Because most of the vaccines have been implemented through the NIP for 10 years in Turkey, 88% of children required these new vaccines or booster doses. Moreover, 86.6% of the children and 92.6% of household contacts had no prior history of influenza vaccine. Furthermore, 88% of the patients had not received the varicella vaccine, and the anti-varicella IgG levels were only negative in 27.9%. In addition, 18.6% of the children were negative for anti-mumps IgG, 23.7% for anti-measles IgG, and 6.3% for anti-rubella IgG. Anti-HBs IgG level was 0-10 IU/L in 45.6% of the patients (most of them previously vaccinated) and 79.8% were negative for hepatitis A IgG antibodies. For pertussis infection, the antibody titers of 54.1% of patients were below the protective level, and 10% of patients had a prior acute pertussis infection. Therefore, it is suggested that children with CND should be evaluated for their vaccination status during their first and follow-up visits at certain intervals, and their primary immunization should be completed; moreover, many will need revaccination or booster doses.

  17. Sulphonylurea usage in melioidosis is associated with severe disease and suppressed immune response.

    Directory of Open Access Journals (Sweden)

    Xiang Liu

    2014-04-01

    Full Text Available BACKGROUND: Melioidosis is a problem in the developing tropical regions of Southeast Asia and Northern Australia where the the Gram negative saprophytic bacillus Burkholderia pseudomallei is endemic with the risk of fulminant septicaemia. While diabetes mellitus is a well-established risk factor for melioidiosis, little is known if specific hypoglycemic agents may differentially influence the susceptibility and clinical course of infection with B. pseudomallei (Bp. METHODOLOGY/PRINCIPAL FINDINGS: In this cohort study, patients with pre-existing diabetes and melioidosis were retrospectively studied. OUTCOME MEASURES: mortality, length of stay and development of complications (namely hypotension, intubation, renal failure and septicaemia were studied in relation to prior diabetic treatment regimen. Peripheral blood mononuclear cells (PBMC from diabetic patients and healthy PBMC primed with metformin, glyburide and insulin were stimulated with purified Bp antigens in vitro. Immune response and specific immune pathway mediators were studied to relate to the clinical findings mechanistically. Of 74 subjects, 44 (57.9% had sulphonylurea-containing diabetic regimens. Patient receiving sulphonylureas had more severe septic complications (47.7% versus 16.7% p = 0.006, in particular, hypotension requiring intropes (p = 0.005. There was also a trend towards increased mortality in sulphonylurea-users (15.9% versus 3.3% p = 0.08. In-vitro, glyburide suppressed inflammatory cytokine production in a dose-dependent manner. An effect of the drug was the induction of IL-1R-associated kinase-M at the level of mRNA transcription. CONCLUSION/SIGNIFICANCE: Sulphonylurea treatment results in suppression of host inflammatory response and may put patients at higher risk for adverse outcomes in melioidosis.

  18. Multistudy fine mapping of chromosome 2q identifies XRCC5 as a chronic obstructive pulmonary disease susceptibility gene

    DEFF Research Database (Denmark)

    Hersh, Craig P; Pillai, Sreekumar G; Zhu, Guohua

    2010-01-01

    to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q. METHODS: Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from...... the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families...

  19. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    International Nuclear Information System (INIS)

    Park, J.E.S.; Beal, I.; Dilworth, J.P.; Tormey, V.; Haddock, J.

    2005-01-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly

  20. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.E.S. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Beal, I. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Dilworth, J.P. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Tormey, V. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Haddock, J. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom)]. E-mail: jamandahaddock@royalfree.nhs.uk

    2005-06-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly.