Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

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Kelly Ben L

2010-02-01

Full Text Available Abstract Background Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen Leishmania has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of Leishmania-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease. Methods We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of Leishmania using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of Leishmania uptake on LPS-induced cytokine expression with uptake of inert latex beads. Results Whilst Leishmania uptake alone did not induce significant levels of any cytokine analysed in this study, Leishmania uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, L. amazonensis was generally more suppressive than L. major. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during Leishmania uptake, in a parasite-specific manner. Conclusions During uptake by macrophages, Leishmania evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, Leishmania suppresses certain proinflammatory cytokine responses in a parasite

Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii.

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Kimberly M Cirelli

2014-03-01

Full Text Available Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring Toxoplasma resistance in rats was previously mapped to a region of chromosome 10 containing Nlrp1. This gene encodes an inflammasome sensor controlling macrophage sensitivity to anthrax lethal toxin (LT induced rapid cell death (pyroptosis. We show here that rat strain differences in Toxoplasma infected macrophage sensitivity to pyroptosis, IL-1β/IL-18 processing, and inhibition of parasite proliferation are perfectly correlated with NLRP1 sequence, while inversely correlated with sensitivity to anthrax LT-induced cell death. Using recombinant inbred rats, SNP analyses and whole transcriptome gene expression studies, we narrowed the candidate genes for control of Toxoplasma-mediated rat macrophage pyroptosis to four genes, one of which was Nlrp1. Knockdown of Nlrp1 in pyroptosis-sensitive macrophages resulted in higher parasite replication and protection from cell death. Reciprocally, overexpression of the NLRP1 variant from Toxoplasma-sensitive macrophages in pyroptosis-resistant cells led to sensitization of these resistant macrophages. Our findings reveal Toxoplasma as a novel activator of the NLRP1 inflammasome in rat macrophages.

Treatment in vitro with PPARα and PPARγ ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice.

Science.gov (United States)

Penas, Federico; Mirkin, Gerardo A; Vera, Marcela; Cevey, Ágata; González, Cintia D; Gómez, Marisa I; Sales, María Elena; Goren, Nora B

2015-05-01

Trypanosoma cruzi, the etiological agent of Chagas' disease, induces a persistent inflammatory response. Macrophages are a first line cell phenotype involved in the clearance of infection. Upon parasite uptake, these cells increase inflammatory mediators like NO, TNF-α, IL-1β and IL-6, leading to parasite killing. Although desired, inflammatory response perpetuation and exacerbation may lead to tissue damage. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors that, besides regulating lipid and carbohydrate metabolism, have a significant anti-inflammatory effect. This is mediated through the interaction of the receptors with their ligands. PPARγ, one of the PPAR isoforms, has been implicated in macrophage polarization from M1, the classically activated phenotype, to M2, the alternatively activated phenotype, in different models of metabolic disorders and infection. In this study, we show for the first time that, besides PPARγ, PPARα is also involved in the in vitro polarization of macrophages isolated from T. cruzi-infected mice. Polarization was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers like Arginase I, Ym1, mannose receptor and TGF-β. Besides, macrophage phagocytic activity was significantly enhanced, leading to increased parasite load. We suggest that modulation of the inflammatory response by both PPARs might be due, at least in part, to a change in the profile of inflammatory macrophages. The potential use of PPAR agonists as modulators of overt inflammatory response during the course of Chagas' disease deserves further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence

KAUST Repository

Haidar, Malak; Rchiad, ‍ Zineb; Ansari, Hifzur Rahman; Ben Rached, Fathia; Tajeri, Shahin; Latre De Late, Perle; Langsley, Gordon; Pain, Arnab

2018-01-01

Theileria annulata is an apicomplexan parasite that infects and transforms bovine macrophages that disseminate throughout the animal causing a leukaemia-like disease called tropical theileriosis. Using deep RNAseq of T. annulata-infected B cells

Neglected Parasitic Infections: Toxocariasis

Centers for Disease Control (CDC) Podcasts

This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Neglected Parasitic Infections in the United States. Neglected Parasitic Infections are a group of diseases that afflict vulnerable populations and are often not well studied or diagnosed. A subject matter expert from CDC's Division of Parasitic Diseases and Malaria describes the epidemiology, diagnosis, and treatment of toxocariasis.

Neglected Parasitic Infections: Toxocariasis

Centers for Disease Control (CDC) Podcasts

2012-01-05

This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Neglected Parasitic Infections in the United States. Neglected Parasitic Infections are a group of diseases that afflict vulnerable populations and are often not well studied or diagnosed. A subject matter expert from CDC's Division of Parasitic Diseases and Malaria describes the epidemiology, diagnosis, and treatment of toxocariasis.  Created: 1/5/2012 by Center for Global Health, Division of Parasitic Diseases and Malaria (DPDM); Emergency Risk Communication Branch (ERCB)/Joint Information Center (JIC), Office of Public Health Preparedness and Response (OPHPR).   Date Released: 1/9/2012.

Cyclobenzaprine Raises ROS Levels in Leishmania infantum and Reduces Parasite Burden in Infected Mice.

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Edézio Ferreira Cunha-Júnior

2017-01-01

Full Text Available The leishmanicidal action of tricyclic antidepressants has been studied and evidences have pointed that their action is linked to inhibition of trypanothione reductase, a key enzyme in the redox metabolism of pathogenic trypanosomes. Cyclobenzaprine (CBP is a tricyclic structurally related to the antidepressant amitriptyline, differing only by the presence of a double bond in the central ring. This paper describes the effect of CBP in experimental visceral leishmaniasis, its inhibitory effect in trypanothione reductase and the potential immunomodulatory activity.In vitro antileishmanial activity was determined in promastigotes and in L. infantum-infected macrophages. For in vivo studies, L. infantum-infected BALB/c mice were treated with CBP by oral gavage for five days and the parasite load was estimated. Trypanothione reductase activity was assessed in the soluble fraction of promastigotes of L. infantum. For evaluation of cytokines, L. infantum-infected macrophages were co-cultured with BALB/c splenocytes and treated with CBP for 48 h. The supernatant was analyzed for IL-6, IL-10, MCP-1, IFN-γ and TNF-α. CBP demonstrated an IC50 of 14.5±1.1μM and an IC90 of 74.5±1.2 μM in promastigotes and an IC50 of 12.6±1.05 μM and an IC90 of 28.7±1.3 μM in intracellular amastigotes. CBP also reduced the parasite load in L. infantum-infected mice by 40.4±10.3% and 66.7±10.5% in spleen at 24.64 and 49.28 mg/kg, respectively and by 85.6±5.0 and 89.3±4.8% in liver at 24.64 and 49.28mg/kg, after a short-term treatment. CBP inhibited the trypanothione reductase activity with a Ki of 86 ± 7.7 μM and increased the ROS production in promastigotes. CBP inhibited in 53% the production of IL-6 in infected macrophages co-culture.To the best of our knowledge, this study is the first report of the in vivo antileishmanial activity of the FDA-approved drug CBP. Modulation of immune response and induction of oxidative stress in parasite seem to contribute to

Nuclear techniques in the study of parasitic infections

International Nuclear Information System (INIS)

1982-01-01

Out of 57 papers published, 47 fall within the INIS subject scope. Seven main topics were covered: resistance to infections with protozoan parasites; resistance to infections with African trypanosomes and helminths of ruminant animals; resistance to infections with filarial parasites and schistosomes; pathology of parasitic infections; epidemiology and diagnosis of parasitic infections; physiology and biochemistry of parasitic organisms; pharmacodynamics of anti-parasitic agents

Parasitic infections of the external eye.

Science.gov (United States)

Pahuja, Shivani; Puranik, Charuta; Jelliti, Bechir; Khairallah, Moncef; Sangwan, Virender S

2013-08-01

To review the published literature on parasitic infections of external eye. Published articles and case reports on parasitic infections of external eye were reviewed and relevant information was collected. Parasitic infections of the eye are rare. However, being more commonly seen in developing nations, they require active measures for screening, diagnosis, and therapy. Parasites of importance causing external ocular disease are protozoan parasites, such as Leishmania; metazoans, such as nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms); or ectoparasites, such as Phthirus pubis and Demodex.

Extracellular vesicles from Leishmania-infected macrophages confer an anti-infection cytokine-production profile to naïve macrophages.

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André Cronemberger-Andrade

2014-09-01

Full Text Available Extracellular vesicles (EVs are structures with phospholipid bilayer membranes and 100-1000 nm diameters. These vesicles are released from cells upon activation of surface receptors and/or apoptosis. The production of EVs by dendritic cells, mast cells, macrophages, and B and T lymphocytes has been extensively reported in the literature. EVs may express MHC class II and other membrane surface molecules and carry antigens. The aim of this study was to investigate the role of EVs from Leishmania-infected macrophages as immune modulatory particles.In this work it was shown that BALB/c mouse bone marrow-derived macrophages, either infected in vitro with Leishmania amazonensis or left uninfected, release comparable amounts of 50-300 nm-diameter extracellular vesicles (EVs. The EVs were characterized by flow cytometry and electron microscopy. The incubation of naïve macrophages with these EVs for 48 hours led to a statistically significant increase in the production of the cytokines IL-12, IL-1β, and TNF-α.EVs derived from macrophages infected with L. amazonensis induce other macrophages, which in vivo could be bystander cells, to produce the proinflammatory cytokines IL-12, IL-1β and TNF-α. This could contribute both to modulate the immune system in favor of a Th1 immune response and to the elimination of the Leishmania, leading, therefore, to the control the infection.

Distinct Macrophage Fates after in vitro Infection with Different Species of Leishmania: Induction of Apoptosis by Leishmania (Leishmania) amazonensis, but Not by Leishmania (Viannia) guyanensis.

Science.gov (United States)

DaMata, Jarina Pena; Mendes, Bárbara Pinheiro; Maciel-Lima, Kátia; Menezes, Cristiane Alves Silva; Dutra, Walderez Ornelas; Sousa, Lirlândia Pires; Horta, Maria Fátima

2015-01-01

Leishmania is an intracellular parasite in vertebrate hosts, including man. During infection, amastigotes replicate inside macrophages and are transmitted to healthy cells, leading to amplification of the infection. Although transfer of amastigotes from infected to healthy cells is a crucial step that may shape the outcome of the infection, it is not fully understood. Here we compare L. amazonensis and L. guyanensis infection in C57BL/6 and BALB/c mice and investigate the fate of macrophages when infected with these species of Leishmania in vitro. As previously shown, infection of mice results in distinct outcomes: L. amazonensis causes a chronic infection in both strains of mice (although milder in C57BL/6), whereas L. guyanensis does not cause them disease. In vitro, infection is persistent in L. amazonensis-infected macrophages whereas L. guyanensis growth is controlled by host cells from both strains of mice. We demonstrate that, in vitro, L. amazonensis induces apoptosis of both C57BL/6 and BALB/c macrophages, characterized by PS exposure, DNA cleavage into nucleosomal size fragments, and consequent hypodiploidy. None of these signs were seen in macrophages infected with L. guyanensis, which seem to die through necrosis, as indicated by increased PI-, but not Annexin V-, positive cells. L. amazonensis-induced macrophage apoptosis was associated to activation of caspases-3, -8 and -9 in both strains of mice. Considering these two species of Leishmania and strains of mice, macrophage apoptosis, induced at the initial moments of infection, correlates with chronic infection, regardless of its severity. We present evidence suggestive that macrophages phagocytize L. amazonensis-infected cells, which has not been verified so far. The ingestion of apoptotic infected macrophages by healthy macrophages could be a way of amastigote spreading, leading to the establishment of infection.

Distinct Macrophage Fates after in vitro Infection with Different Species of Leishmania: Induction of Apoptosis by Leishmania (Leishmania amazonensis, but Not by Leishmania (Viannia guyanensis.

Directory of Open Access Journals (Sweden)

Jarina Pena DaMata

Full Text Available Leishmania is an intracellular parasite in vertebrate hosts, including man. During infection, amastigotes replicate inside macrophages and are transmitted to healthy cells, leading to amplification of the infection. Although transfer of amastigotes from infected to healthy cells is a crucial step that may shape the outcome of the infection, it is not fully understood. Here we compare L. amazonensis and L. guyanensis infection in C57BL/6 and BALB/c mice and investigate the fate of macrophages when infected with these species of Leishmania in vitro. As previously shown, infection of mice results in distinct outcomes: L. amazonensis causes a chronic infection in both strains of mice (although milder in C57BL/6, whereas L. guyanensis does not cause them disease. In vitro, infection is persistent in L. amazonensis-infected macrophages whereas L. guyanensis growth is controlled by host cells from both strains of mice. We demonstrate that, in vitro, L. amazonensis induces apoptosis of both C57BL/6 and BALB/c macrophages, characterized by PS exposure, DNA cleavage into nucleosomal size fragments, and consequent hypodiploidy. None of these signs were seen in macrophages infected with L. guyanensis, which seem to die through necrosis, as indicated by increased PI-, but not Annexin V-, positive cells. L. amazonensis-induced macrophage apoptosis was associated to activation of caspases-3, -8 and -9 in both strains of mice. Considering these two species of Leishmania and strains of mice, macrophage apoptosis, induced at the initial moments of infection, correlates with chronic infection, regardless of its severity. We present evidence suggestive that macrophages phagocytize L. amazonensis-infected cells, which has not been verified so far. The ingestion of apoptotic infected macrophages by healthy macrophages could be a way of amastigote spreading, leading to the establishment of infection.

Immunity to parasitic infection

National Research Council Canada - National Science Library

Lamb, Tracey J

2012-01-01

... may be manipulated to develop therapeutic interventions against parasitic infection. For easy reference, the most commonly studied parasites are examined in individual chapters written by investigators at the forefront of their field...

HIV Infection of Macrophages: Implications for Pathogenesis and Cure

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Kiera Leigh Clayton

2017-05-01

Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

Macrophage origin limits functional plasticity in helminth-bacterial co-infection.

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Dominik Rückerl

2017-03-01

Full Text Available Rapid reprogramming of the macrophage activation phenotype is considered important in the defense against consecutive infection with diverse infectious agents. However, in the setting of persistent, chronic infection the functional importance of macrophage-intrinsic adaptation to changing environments vs. recruitment of new macrophages remains unclear. Here we show that resident peritoneal macrophages expanded by infection with the nematode Heligmosomoides polygyrus bakeri altered their activation phenotype in response to infection with Salmonella enterica ser. Typhimurium in vitro and in vivo. The nematode-expanded resident F4/80high macrophages efficiently upregulated bacterial induced effector molecules (e.g. MHC-II, NOS2 similarly to newly recruited monocyte-derived macrophages. Nonetheless, recruitment of blood monocyte-derived macrophages to Salmonella infection occurred with equal magnitude in co-infected animals and caused displacement of the nematode-expanded, tissue resident-derived macrophages from the peritoneal cavity. Global gene expression analysis revealed that although nematode-expanded resident F4/80high macrophages made an anti-bacterial response, this was muted as compared to newly recruited F4/80low macrophages. However, the F4/80high macrophages adopted unique functional characteristics that included enhanced neutrophil-stimulating chemokine production. Thus, our data provide important evidence that plastic adaptation of MΦ activation does occur in vivo, but that cellular plasticity is outweighed by functional capabilities specific to the tissue origin of the cell.

Helminth parasites alter protection against Plasmodium infection.

Science.gov (United States)

Salazar-Castañon, Víctor H; Legorreta-Herrera, Martha; Rodriguez-Sosa, Miriam

2014-01-01

More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

Pitting of malaria parasites and spherocyte formation

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Gichuki Charity W

2006-07-01

Full Text Available Abstract Background A high prevalence of spherocytes was detected in blood smears of children enrolled in a case control study conducted in the malaria holoendemic Lake Victoria basin. It was speculated that the spherocytes reflect intraerythrocytic removal of malarial parasites with a concurrent removal of RBC membrane through a process analogous to pitting of intraerythrocytic inclusion bodies. Pitting and re-circulation of RBCs devoid of malaria parasites could be a host mechanism for parasite clearance while minimizing the anaemia that would occur were the entire parasitized RBC removed. The prior demonstration of RBCs containing ring-infected erythrocyte surface antigen (pf 155 or RESA but no intracellular parasites, support the idea of pitting. Methods An in vitro model was developed to examine the phenomenon of pitting and spherocyte formation in Plasmodium falciparum infected RBCs (iRBC co-incubated with human macrophages. In vivo application of this model was evaluated using blood specimens from patients attending Kisumu Ditrict Hospital. RBCs were probed with anti-RESA monoclonal antibody and a DNA stain (propidium iodide. Flow cytometry and fluorescent microscopy was used to compare RBCs containing both the antigen and the parasites to those that were only RESA positive. Results Co-incubation of iRBC and tumor necrosis factor-alpha activated macrophages led to pitting (14% ± 1.31% macrophages with engulfed trophozoites as opposed to erythrophagocytosis (5.33% ± 0.95% (P Conclusion It is proposed that in malaria holoendemic areas where prevalence of asexual stage parasites approaches 100% in children, RBCs with pitted parasites are re-circulated and pitting may produce spherocytes.

Polarized M2 macrophages in dogs with visceral leishmaniasis.

Science.gov (United States)

Moreira, Pamela Rodrigues Reina; Fernando, Filipe Santos; Montassier, Hélio José; André, Marcos Rogério; de Oliveira Vasconcelos, Rosemeri

2016-08-15

The objective of the present study was to analyze the skin (nasal surface and ear regions), lymph nodes (popliteal and pre-scapular), spleen and liver of dogs with visceral leishmaniasis (VL), in order to investigate the relationship between the parasite load measured as DNA copy number of Alpha gene of DNA polymerase of Leishmania infantum by quantitative PCR and the number of M2 macrophages by immunohistochemistry. A set of 29 naturally infected dogs from an endemic area for VL were sampled and another set of six dogs negative for VL and from a non-endemic area were analyzed as the control group (C). The spleen presented the highest number of Leishmania DNA copies, with significant differences between the groups G1 and G2 (with and without skin lesions, respectively). The M2 phenotype immunostaining predominated among the macrophages in granulomas and inflammatory infiltrates of samples from the skin, lymph nodes and spleens examined. The presence of M2 macrophages in dogs from infected group differed significantly from the control group, in all organs analyzed, excepted liver. The highest proportion of M2 macrophages coincided with the highest parasitism loads found in more susceptible organs of VL dogs, even in the skin, considered a more resistant organ, while the liver showed low parasitism load and low immunostaining for M2 macrophages with no significant differences between infected and negative groups. It was concluded that the predominance of M2 phenotype in VL dogs favored the multiplication of Leishmania infantum in organs of dogs that are more susceptible to Leishmania infection, as skin, lymph nodes and spleen. Copyright © 2016 Elsevier B.V. All rights reserved.

Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

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Stephen H-F Macdonald

Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum

Science.gov (United States)

Teixeira, Luzia; Moreira, João; Melo, Joana; Bezerra, Filipa; Marques, Raquel M; Ferreirinha, Pedro; Correia, Alexandra; Monteiro, Mariana P; Ferreira, Paula G; Vilanova, Manuel

2015-01-01

The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet+ cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue. PMID:25581844

Salivary Gland Extract Modulates the Infection of Two Leishmania enriettii Strains by Interfering With Macrophage Differentiation in the Model of Cavia porcellus

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Lucélia J. Pinheiro

2018-05-01

Full Text Available The subgenus Mundinia includes several Leishmania species that have human and veterinary importance. One of those members, Leishmania Mundinia enriettii was isolated from the guinea pig Cavia porcellus in the 1940s. Several histopathological studies have already been performed in this species in the absence of salivary gland extract (SGE, which are determinant and the early and future events of the infection. Our main hypothesis is that SGE could differentially modulate the course of the lesion and macrophage differentiation caused by avirulent and virulent L. enriettii strains. Here, the C. porcellus nasal region was infected using needles with two strains of L. enriettii (L88 and Cobaia in the presence/absence of SGE and followed for 12 weeks. Those strains vary in terms of virulence, and their histopathological development was characterized. Some L88-infected animals could develop ulcerated/nodular lesions, whereas Cobaia strain developed non-ulcerated nodular lesions. Animals experimentally inoculated developed a protuberance and/or lesion after the 4th and 5th weeks of infection. Macroscopically, the size of lesion in L88-infected animals was smaller in the presence of SGE. Remarkable differences were detected microscopically in the presence of SGE for both strains. After the 6th and 7th weeks, L88-infected animals were heavily parasitized with an intense inflammatory profile bearing amastigotes and pro-inflammatory cells compared to those infected by Cobaia strain. Morphometry analysis revealed that L1+ macrophages were abundant in the L88 infection, but not in the Cobaia infection. In the presence of SGE, an increased CD163+ macrophage infiltrate by both strains was detected. Interestingly, this effect was more pronounced in Cobaia-infected animals. This study showed the role of SGE during the course of L. enriettii (strains L88 and Cobaia infection and its role in modulating macrophage attraction to the lesion site. SGE decreased L1

The influence of macrophage growth factors on Theiler's Murine Encephalomyelitis Virus (TMEV) infection and activation of macrophages.

Science.gov (United States)

Schneider, Karin M; Watson, Neva B; Minchenberg, Scott B; Massa, Paul T

2018-02-01

Macrophages are common targets for infection and innate immune activation by many pathogenic viruses including the neurotropic Theiler's Murine Encephalomyelitis Virus (TMEV). As both infection and innate activation of macrophages are key determinants of viral pathogenesis especially in the central nervous system (CNS), an analysis of macrophage growth factors on these events was performed. C3H mouse bone-marrow cells were differentiated in culture using either recombinant macrophage colony stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), inoculated with TMEV (BeAn) and analyzed at various times thereafter. Cytokine RNA and protein analysis, virus titers, and flow cytometry were performed to characterize virological parameters under these culture conditions. GM-CSF-differentiated macrophages showed higher levels of TMEV viral RNA and proinflammatory molecules compared to infected M-CSF-differentiated cells. Thus, GM-CSF increases both TMEV infection and TMEV-induced activation of macrophages compared to that seen with M-CSF. Moreover, while infectious viral particles decreased from a peak at 12h to undetectable levels at 48h post infection, TMEV viral RNA remained higher in GM-CSF- compared to M-CSF-differentiated macrophages in concert with increased proinflammatory gene expression. Analysis of a possible basis for these differences determined that glycolytic rates contributed to heightened virus replication and proinflammatory cytokine secretion in GM-CSF compared to M-CSF-differentiated macrophages. In conclusion, we provide evidence implicating a role for GM-CSF in promoting virus replication and proinflammatory cytokine expression in macrophages, indicating that GM-CSF may be a key factor for TMEV infection and the induction of chronic TMEV-induced immunopathogenesis in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites.

Science.gov (United States)

Badirzadeh, Alireza; Taheri, Tahereh; Taslimi, Yasaman; Abdossamadi, Zahra; Heidari-Kharaji, Maryam; Gholami, Elham; Sedaghat, Baharehsadat; Niyyati, Maryam; Rafati, Sima

2017-07-01

Proliferation of Leishmania (L.) parasites depends on polyamine availability, which can be generated by the L-arginine catabolism and the enzymatic activity of arginase (ARG) of the parasites and of the mammalian hosts. In the present study, we characterized and compared the arginase (arg) genes from pathogenic L. major and L. tropica and from non-pathogenic L. tarentolae. We quantified the level of the ARG activity in promastigotes and macrophages infected with pathogenic L. major and L. tropica and non-pathogenic L. tarentolae amastigotes. The ARG's amino acid sequences of the pathogenic and non-pathogenic Leishmania demonstrated virtually 98.6% and 88% identities with the reference L. major Friedlin ARG. Higher ARG activity was observed in all pathogenic promastigotes as compared to non-pathogenic L. tarentolae. In vitro infection of human macrophage cell line (THP1) with pathogenic and non-pathogenic Leishmania spp. resulted in increased ARG activities in the infected macrophages. The ARG activities present in vivo were assessed in susceptible BALB/c and resistant C57BL/6 mice infected with L. major, L. tropica and L. tarentolae. We demonstrated that during the development of the infection, ARG is induced in both strains of mice infected with pathogenic Leishmania. However, in L. major infected BALB/c mice, the induction of ARG and parasite load increased simultaneously according to the time course of infection, whereas in C57BL/6 mice, the enzyme is upregulated solely during the period of footpad swelling. In L. tropica infected mice, the footpads' swellings were slow to develop and demonstrated minimal cutaneous pathology and ARG activity. In contrast, ARG activity was undetectable in mice inoculated with the non-pathogenic L. tarentolae. Our data suggest that infection by Leishmania parasites can increase ARG activity of the host and provides essential polyamines for parasite salvage and its replication. Moreover, the ARG of Leishmania is vital for parasite

Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

KAUST Repository

Roy, Sugata; Schmeier, Sebastian; Kaczkowski, Bogumil; Arner, Erik; Alam, Tanvir; Ozturk, Mumin; Tamgue, Ousman; Parihar, Suraj P.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Guler, Reto; Bajic, Vladimir B.; Brombacher, Frank; Suzuki, Harukazu

2018-01-01

landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene

TRANSCRIPTIONAL INHIBITION OF INTERLEUKIN-12 PROMOTER ACTIVITY IN LEISHMANIA SPP.-INFECTED MACROPHAGES

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Jayakumar, Asha; Widenmaier, Robyn; Ma, Xiaojing; McDowell, Mary Ann

2009-01-01

To establish and persist within a host, Leishmania spp. parasites delay the onset of cell-mediated immunity by suppressing interleukin-12 (IL-12) production from host macrophages. Although it is established that Leishmania spp.-infected macrophages have impaired IL-12 production, the mechanisms that account for this suppression remain to be completely elucidated. Using a luciferase reporter assay assessing IL-12 transcription, we report here that Leishmania major, Leishmania donovani, and Leishmania chagasi inhibit IL-12 transcription in response to interferon-gamma, lipopolysaccharide, and CD40 ligand and that Leishmania spp. lipophosphoglycan, phosphoglycans, and major surface protein are not necessary for inhibition. In addition, all the Leishmania spp. strains and life-cycle stages tested inhibited IL-12 promoter activity. Our data further reveal that autocrine-acting host factors play no role in the inhibitory response and that phagocytosis signaling is necessary for inhibition of IL-12. PMID:18372625

Impaired chromatin remodelling at STAT1-regulated promoters leads to global unresponsiveness of Toxoplasma gondii-infected macrophages to IFN-γ.

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Christine Lang

2012-01-01

Full Text Available Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ stimulated with interferon (IFN-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma-infected

Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

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Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

2018-05-01

Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.

Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

KAUST Repository

Roy, Sugata

2018-04-24

Mycobacterium tuberculosis (Mtb) infection reveals complex and dynamic host-pathogen interactions, leading to host protection or pathogenesis. Using a unique transcriptome technology (CAGE), we investigated the promoter-based transcriptional landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene Ontology enrichment analysis for Mtb-induced differentially expressed genes revealed various terms, related to host-protection and inflammation, enriched in up-regulated genes. On the other hand, terms related to dis-regulation of cellular functions were enriched in down-regulated genes. Differential expression analysis revealed known as well as novel transcription factor genes in Mtb infection, many of them significantly down-regulated. IFNγ or IL-4/IL-13 pre-stimulation induce additional differentially expressed genes in Mtb-infected macrophages. Cluster analysis uncovered significant numbers, prolonging their expressional changes. Furthermore, Mtb infection augmented cytokine-mediated M1 and M2 pre-activations. In addition, we identified unique transcriptional features of Mtb-mediated differentially expressed lncRNAs. In summary we provide a comprehensive in depth gene expression/regulation profile in Mtb-infected macrophages, an important step forward for a better understanding of host-pathogen interaction dynamics in Mtb infection.

Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.

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Costa, Mônica S; Gonçalves, Yasmim G; Nunes, Débora C O; Napolitano, Danielle R; Maia, Pedro I S; Rodrigues, Renata S; Rodrigues, Veridiana M; Von Poelhsitz, Gustavo; Yoneyama, Kelly A G

2017-10-01

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis‑[Ru II (η 2 -O 2 CR)(dppm) 2 ]PF 6 , with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC 50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC 50 values ranged from 7.52-12.59μM (complex 1); 0.70-3.28μM (complex 2) and 0.52-1.75μM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence

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Haidar, Malak

2018-03-23

Theileria annulata is an apicomplexan parasite that infects and transforms bovine macrophages that disseminate throughout the animal causing a leukaemia-like disease called tropical theileriosis. Using deep RNAseq of T. annulata-infected B cells and macrophages we identify a set of microRNAs induced by infection, whose expression diminishes upon loss of the hyper-disseminating phenotype of virulent transformed macrophages. We describe how infection-induced upregulation of miR-126-5p ablates JIP-2 expression to release cytosolic JNK to translocate to the nucleus and trans-activate AP-1-driven transcription of mmp9 to promote tumour dissemination. In non-disseminating attenuated macrophages miR-126-5p levels drop, JIP-2 levels increase, JNK1 is retained in the cytosol leading to decreased c-Jun phosphorylation and dampened AP-1-driven mmp9 transcription. We show that variation in miR-126-5p levels depends on the tyrosine phosphorylation status of AGO2 that is regulated by Grb2-recruitment of PTP1B. In attenuated macrophages Grb2 levels drop resulting in less PTP1B recruitment, greater AGO2 phosphorylation, less miR-126-5p associated with AGO2 and a consequent rise in JIP-2 levels. Changes in miR-126-5p levels therefore, underpin both the virulent hyper-dissemination and the attenuated dissemination of T. annulata-infected macrophages.

Liver macrophages: friend or foe during hepatitis B infection?

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Faure-Dupuy, Suzanne; Durantel, David; Lucifora, Julie

2018-05-17

The Hepatitis B virus chronically infects the liver of 250 million people worldwide. Over the past decades, major advances have been made in the understanding of Hepatitis B virus life cycle in hepatocytes. Beside these parenchymal cells, the liver also contains resident and infiltrating myeloid cells involved in immune responses to pathogens and much less is known about their interplay with Hepatitis B virus. In this review, we summarized and discussed the current knowledge of the role of liver macrophages (including Kupffer cells and liver monocyte-derived macrophages), in HBV infection. While it is still unclear if liver macrophages play a role in the establishment and persistence of HBV infection, several studies disclosed data suggesting that HBV would favour liver macrophage anti-inflammatory phenotypes and thereby increase liver tolerance. In addition, alternatively activated liver macrophages might also play in the long term a key role in hepatitis B associated pathogenesis, especially through the activation of hepatic stellate cells. Therapies aiming at a transient activation of pro-inflammatory liver macrophages should therefore be considered for the treatment of chronic HBV infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages.

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Petersen, Antonio Luis de Oliveira Almeida; Guedes, Carlos Eduardo Sampaio; Versoza, Carolina Leite; Lima, José Geraldo Bomfim; de Freitas, Luiz Antônio Rodrigues; Borges, Valéria Matos; Veras, Patrícia Sampaio Tavares

2012-01-01

Leishmaniasis is a neglected endemic disease with a broad spectrum of clinical manifestations. Pentavalent antimonials have been the treatment of choice for the past 70 years and, due to the emergence of resistant cases, the efficacy of these drugs has come under scrutiny. Second-line drugs are less efficacious, cause a range of side effects and can be costly. The formulation of new generations of drugs, especially in developing countries, has become mandatory. We investigated the anti-leishmanial effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor, in vitro. This inhibitor is currently in clinical trials for cancer treatment; however, its effects against intracellular Leishmania remain untested. Macrophages infected with L. amazonensis were treated with 17-AAG (25-500 nM) and parasite load was quantified using optical microscopy. Parasite load declined in 17-AAG-treated macrophages in a dose- and time-dependent manner. Intracellular parasite death became irreversible after 4 h of treatment with 17-AAG, and occurred independent of nitric oxide (NO) and superoxide (O(2) (-)) production. Additionally, intracellular parasite viability was severely reduced after 48 h of treatment. Interestingly, treatment with 17-AAG reduced pro-inflammatory mediator production, including TNF-α, IL-6 and MCP-1, yet IL-12 remained unaffected. Electron microscopy revealed morphological alterations, such as double-membrane vacuoles and myelin figures at 24 and 48 h after 17-AAG treatment. The HSP90 inhibitor, 17-AAG, possesses high potency under low dosage and reduces both pro-inflammatory and oxidative molecule production. Therefore, further studies are warranted to investigate this inhibitor's potential in the development of new generations of anti-leishmanials.

Micro RNA in Exosomes from HIV-Infected Macrophages

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William W. Roth

2015-12-01

Full Text Available Exosomes are small membrane-bound vesicles secreted by cells that function to shuttle RNA and proteins between cells. To examine the role of exosomal micro RNA (miRNA during the early stage of HIV-1 infection we characterized miRNA in exosomes from HIV-infected macrophages, compared with exosomes from non-infected macrophages. Primary human monocytes from uninfected donors were differentiated to macrophages (MDM which were either mock-infected or infected with the macrophage-tropic HIV-1 BaL strain. Exosomes were recovered from culture media and separated from virus particles by centrifugation on iodixanol density gradients. The low molecular weight RNA fraction was prepared from purified exosomes. After pre-amplification, RNA was hybridized to microarrays containing probes for 1200 miRNA species of known and unknown function. We observed 48 miRNA species in both infected and uninfected MDM exosomes. Additionally, 38 miRNAs were present in infected-cell exosomes but not uninfected-cell exosomes. Of these, 13 miRNAs were upregulated in exosomes from HIV-infected cells, including 4 miRNA species that were increased by more than 10-fold. Though numerous miRNA species have been identified in HIV-infected cells, relatively little is known about miRNA content in exosomes from these cells. In the future, we plan to investigate whether the upregulated miRNA species we identified are increased in exosomes from HIV-1-positive patients.

Changes in Macrophage Gene Expression Associated with Leishmania (Viannia braziliensis Infection.

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Clemencia Ovalle-Bracho

Full Text Available Different Leishmania species cause distinct clinical manifestations of the infectious disease leishmaniasis. It is fundamentally important to understand the mechanisms governing the interaction between Leishmania and its host cell. Little is known about this interaction between Leishmania (Viannia braziliensis and human macrophages. In this study, we aimed to identify differential gene expression between non-infected and L. (V braziliensis-infected U937-derived macrophages. We deployed a whole human transcriptome microarray analysis using 72 hours post-infection samples and compared those samples with their non-infected counterparts. We found that 218 genes were differentially expressed between infected and non-infected macrophages. A total of 71.6% of these genes were down-regulated in the infected macrophages. Functional enrichment analyses identified the steroid and sterol/cholesterol biosynthetic processes between regulatory networks down-regulated in infected macrophages. RT-qPCR further confirmed this down-regulation in genes belonging to these pathways. These findings contrast with those from studies involving other Leishmania species at earlier infection stages, where gene up-regulation for this metabolic pathway has been reported. Sterol biosynthesis could be an important biological process associated with the expression profile of macrophages infected by L. (V. braziliensis. Differential transcriptional results suggest a negative regulation of the genetic regulatory network involved in cholesterol biosynthesis.

Strain specific transcriptional response in Mycobacterium tuberculosis infected macrophages

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Koo Mi-Sun

2012-01-01

Full Text Available Abstract Background Tuberculosis (TB, a bacterial infection caused by Mycobacterium tuberculosis (Mtb remains a significant health problem worldwide with a third of the world population infected and nearly nine million new cases claiming 1.1 million deaths every year. The outcome following infection by Mtb is determined by a complex and dynamic host-pathogen interaction in which the phenotype of the pathogen and the immune status of the host play a role. However, the molecular mechanism by which Mtb strains induce different responses during intracellular infection of the host macrophage is not fully understood. To explore the early molecular events triggered upon Mtb infection of macrophages, we studied the transcriptional responses of murine bone marrow-derived macrophages (BMM to infection with two clinical Mtb strains, CDC1551 and HN878. These strains have previously been shown to differ in their virulence/immunogenicity in the mouse and rabbit models of pulmonary TB. Results In spite of similar intracellular growth rates, we observed that compared to HN878, infection by CDC1551 of BMM was associated with an increased global transcriptome, up-regulation of a specific early (6 hours immune response network and significantly elevated nitric oxide production. In contrast, at 24 hours post-infection of BMM by HN878, more host genes involved in lipid metabolism, including cholesterol metabolism and prostaglandin synthesis were up-regulated, compared to infection with CDC1551. In association with the differences in the macrophage responses to infection with the 2 Mtb strains, intracellular CDC1551 expressed higher levels of stress response genes than did HN878. Conclusions In association with the early and more robust macrophage activation, intracellular CDC1551 cells were exposed to a higher level of stress leading to increased up-regulation of the bacterial stress response genes. In contrast, sub-optimal activation of macrophages and induction of

Role of Tellurite Resistance Operon in Filamentous Growth of Yersinia pestis in Macrophages.

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Ponnusamy, Duraisamy; Clinkenbeard, Kenneth D

2015-01-01

Yersinia pestis initiates infection by parasitism of host macrophages. In response to macrophage infections, intracellular Y. pestis can assume a filamentous cellular morphology which may mediate resistance to host cell innate immune responses. We previously observed the expression of Y. pestis tellurite resistance proteins TerD and TerE from the terZABCDE operon during macrophage infections. Others have observed a filamentous response associated with expression of tellurite resistance operon in Escherichia coli exposed to tellurite. Therefore, in this study we examine the potential role of Y. pestis tellurite resistance operon in filamentous cellular morphology during macrophage infections. In vitro treatment of Y. pestis culture with sodium tellurite (Na2TeO3) caused the bacterial cells to assume a filamentous phenotype similar to the filamentous phenotype observed during macrophage infections. A deletion mutant for genes terZAB abolished the filamentous morphologic response to tellurite exposure or intracellular parasitism, but without affecting tellurite resistance. However, a terZABCDE deletion mutant abolished both filamentous morphologic response and tellurite resistance. Complementation of the terZABCDE deletion mutant with terCDE, but not terZAB, partially restored tellurite resistance. When the terZABCDE deletion mutant was complemented with terZAB or terCDE, Y. pestis exhibited filamentous morphology during macrophage infections as well as while these complemented genes were being expressed under an in vitro condition. Further in E. coli, expression of Y. pestis terZAB, but not terCDE, conferred a filamentous phenotype. These findings support the role of Y. pestis terZAB mediation of the filamentous response phenotype; whereas, terCDE confers tellurite resistance. Although the beneficial role of filamentous morphological responses by Y. pestis during macrophage infections is yet to be fully defined, it may be a bacterial adaptive strategy to macrophage

Listeria monocytogenes infection of HD11, chicken macrophage-like cells.

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Jarvis, N A; Donaldson, J R; O'Bryan, C A; Ricke, S C; Crandall, P G

2017-04-01

Listeria monocytogenes can be carried by and infect poultry, although the clinical disease in birds is rare. Escape from macrophage phagocytosis is a key step in pathogenesis for L. monocytogenes. Therefore, we investigated the infection of the chicken macrophage-like cell line HD11 with 2 strains of L. monocytogenes EGD-e and Scott A. After infection, L. monocytogenes was quantified by spread plating and HD11 was quantified with trypan blue exclusion stain before enumeration. The standard macrophage killing protocols require washing the cell monolayers 3 times with PBS, which was found to negatively influence HD11 monolayers. Maximum bacterial densities within macrophages were not different between the 2 Listeria strains. HD11 required more than 11 h to effectively reduce intracellular L. monocytogenes Scott A, and Scott A was more susceptible to HD11 killing than EGD-e. It appears that Listeria infection initially causes attenuation of HD11 growth, and infected HD11 cells do not begin to lyse until at least 11 h post infection. These results suggest that there are subtle strain to strain differences in response to HD11 macrophage phagocytosis. The long lead-time required for HD11 to kill L. monocytogenes cells means that there is sufficient time available for chicken macrophages to circulate in the blood and transfer the intracellular Listeria to multiple tissues. © 2016 Poultry Science Association Inc.

Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility.

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Barrera, Maria Claudia; Rojas, Laura Jimena; Weiss, Austin; Fernandez, Olga; McMahon-Pratt, Diane; Saravia, Nancy G; Gomez, Maria Adelaida

2017-12-01

The mechanisms of Leishmania resistance to antimonials have been primarily determined in experimentally derived Leishmania strains. However, their participation in the susceptibility phenotype in field isolates has not been conclusively established. Being an intracellular parasite, the activity of antileishmanials is dependent on internalization of drugs into host cells and effective delivery to the intracellular compartments inhabited by the parasite. In this study we quantified and comparatively analyzed the gene expression of nine molecules involved in mechanisms of xenobiotic detoxification and Leishmania resistance to antimonial drugs in resistant and susceptible laboratory derived and clinical L.(Viannia) panamensis strains(n=19). In addition, we explored the impact of Leishmania susceptibility to antimonials on the expression of macrophage gene products having putative functions in transport, accumulation and metabolism of antimonials. As previously shown for other Leishmania species, a trend of increased abcc3 and lower aqp-1 expression was observed in the laboratory derived Sb-resistant L.(V.) panamensis line. However, this was not found in clinical strains, in which the expression of abca2 was significantly higher in resistant strains as both, promastigotes and intracellular amastigotes. The effect of drug susceptibility on host cell gene expression was evaluated on primary human macrophages from patients with cutaneous leishmaniasis (n=17) infected ex-vivo with the matched L.(V.) panamensis strains isolated at diagnosis, and in THP-1 cells infected with clinical strains (n=6) and laboratory adapted L.(V.) panamensis lines. Four molecules, abcb1 (p-gp), abcb6, aqp-9 and mt2a were differentially modulated by drug resistant and susceptible parasites, and among these, a consistent and significantly increased expression of the xenobiotic scavenging molecule mt2a was observed in macrophages infected with Sb-susceptible L. (V.) panamensis. Our results

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

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Gazzinelli R.T.

1998-01-01

Full Text Available Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host. Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Chlamydia pneumoniae hides inside apoptotic neutrophils to silently infect and propagate in macrophages.

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Jan Rupp

Full Text Available BACKGROUND: Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae. METHODOLOGY/PRINCIPAL FINDINGS: We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ss production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-alpha response. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host.

Down regulation of macrophage IFNGR1 exacerbates systemic L. monocytogenes infection.

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Emily M Eshleman

2017-05-01

Full Text Available Interferons (IFNs target macrophages to regulate inflammation and resistance to microbial infections. The type II IFN (IFNγ acts on a cell surface receptor (IFNGR to promote gene expression that enhance macrophage inflammatory and anti-microbial activity. Type I IFNs can dampen macrophage responsiveness to IFNγ and are associated with increased susceptibility to numerous bacterial infections. The precise mechanisms responsible for these effects remain unclear. Type I IFNs silence macrophage ifngr1 transcription and thus reduce cell surface expression of IFNGR1. To test how these events might impact macrophage activation and host resistance during bacterial infection, we developed transgenic mice that express a functional FLAG-tagged IFNGR1 (fGR1 driven by a macrophage-specific promoter. Macrophages from fGR1 mice expressed physiologic levels of cell surface IFNGR1 at steady state and responded equivalently to WT C57Bl/6 macrophages when treated with IFNγ alone. However, fGR1 macrophages retained cell surface IFNGR1 and showed enhanced responsiveness to IFNγ in the presence of type I IFNs. When fGR1 mice were infected with the bacterium Listeria monocytogenes their resistance was significantly increased, despite normal type I and II IFN production. Enhanced resistance was dependent on IFNγ and associated with increased macrophage activation and antimicrobial function. These results argue that down regulation of myeloid cell IFNGR1 is an important mechanism by which type I IFNs suppress inflammatory and anti-bacterial functions of macrophages.

Brucella infection inhibits macrophages apoptosis via Nedd4-dependent degradation of calpain2.

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Cui, Guimei; Wei, Pan; Zhao, Yuxi; Guan, Zhenhong; Yang, Li; Sun, Wanchun; Wang, Shuangxi; Peng, Qisheng

2014-11-07

The calcium-dependent protease calpain2 is involved in macrophages apoptosis. Brucella infection-induced up-regulation of intracellular calcium level is an essential factor for the intracellular survival of Brucella within macrophages. Here, we hypothesize that calcium-dependent E3 ubiquitin ligase Nedd4 ubiquitinates calpain2 and inhibits Brucella infection-induced macrophage apoptosis via degradation of calpain2.Our results reveal that Brucella infection induces increases in Nedd4 activity in an intracellular calcium dependent manner. Furthermore, Brucella infection-induced degradation of calpain2 is mediated by Nedd4 ubiquitination of calpain2. Brucella infection-induced calpain2 degradation inhibited macrophages apoptosis. Treatment of Brucella infected macrophages with calcium chelator BAPTA or Nedd4 knock-down decreased Nedd4 activity, prevented calpain2 degradation, and resulted in macrophages apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

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Karl J Staples

Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

The absence of MyD88 has no effect on the induction of alternatively activated macrophage during Fasciola hepatica infection

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Luo HongLin

2011-11-01

Full Text Available Abstract Background Alternatively activated macrophages (AAMϕ play important roles in allergies and responses to parasitic infections. However, whether signaling through toll-like receptors (TLRs plays any role in AAMϕ induction when young Fasciola hepatica penetrates the liver capsule and migrates through the liver tissue is still unclear. Results The data show that the lack of myeloid differentiation factor 88 (MyD88 has no effect on the AAMϕ derived from the bone marrow (BMMϕ in vitro and does not impair the mRNA expression of arginase-1, resistin-like molecule (RELMα, and Ym1 in BMMϕs. The Th2 cytokine production bias in splenocytes was not significantly altered in F. hepatica-infected mice in the absence of MyD88 in vitro and in the pleural cavity lavage in vivo. In addition, MyD88-deficiency has no effect on the arginase production of the F. hepatica elicited macrophages (Fe Mϕs, production of RELMα and Ym1 proteins and mRNA expression of Ym1 and RELMα of macrophages in the peritoneal cavity 6 weeks post F. hepatica infection. Conclusions The absence of MyD88 has no effect on presence of AAMϕ 6 weeks post F. hepatica infection.

Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy

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Chakrabarti, Saikat; Roy, Syamal

2016-01-01

Background Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation. Methodology/Principal Findings MΦ of CBA/j mice were infected with Leishmania donovani (I-MΦ). Two different anti-Aκ mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5–2) was conformation specific, whereas the other one (10.2.16) was not. Under parasitized condition, the binding of 11.5–2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5–2 was restored to normal upon liposomal delivery of cholesterol in I-MΦ. By molecular dynamics (MD) simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-MΦ. Conclusion The decrease in membrane cholesterol in I-MΦ may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of

Development of ostrich thrombocytes and monocyte-derived macrophages in culture and the control of Toxoplasma gondii reproduction after macrophage activation.

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Miranda, Farlen J B; Damasceno-Sá, João Cláudio; DaMatta, Renato A

2016-01-01

Raising ostriches became an important economic activity after their products became commodities. The health of farm animals is of paramount importance, so assessing basic immunological responses is necessary to better understand health problems. We developed a method to obtain ostrich thrombocytes and macrophages. The thrombocytes died by apoptosis after 48 h in culture, and the macrophages expanded in size and increased the number of acidic compartments. Macrophages were activated by chicken interferon-γ, producing high levels of nitric oxide. Toxoplasma gondii was able to infect these macrophages, and activation controlled parasitic reproduction. T. gondii, however, persisted in these cells, and infection reduced the production of nitric oxide. These results are important for the future assessment of the basic cellular and immunobiology of ostriches and demonstrate T. gondii suppression of nitric oxide production. © 2016 Poultry Science Association Inc.

Mouse adenovirus type 1 infection of macrophages

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Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

2009-01-01

Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

Fecal Occult Blood Test and Gastrointestinal Parasitic Infection

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Majed H. Wakid

2010-01-01

Full Text Available Stool specimens of 1238 workers in western region of Saudi Arabia were examined for infection with intestinal parasites and for fecal occult blood (FOB to investigate the possibility that enteroparasites correlate to occult intestinal bleeding. Direct smears and formal ether techniques were used for detection of diagnostic stages of intestinal parasites. A commercially available guaiac test was used to detect fecal occult blood. 47.01% of the workers were infected with intestinal parasites including eight helminthes species and eight protozoan species. The results provided no significant evidence (P-value=0.143 that intestinal parasitic infection is in association with positive guaiac FOB test.

Host age modulates parasite infectivity, virulence and reproduction.

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Izhar, Rony; Ben-Ami, Frida

2015-07-01

Host age is one of the most striking differences among hosts within most populations, but there is very little data on how age-dependent effects impact ecological and evolutionary dynamics of both the host and the parasite. Here, we examined the influence of host age (juveniles, young and old adults) at parasite exposure on host susceptibility, fecundity and survival as well as parasite transmission, using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa. Younger D. magna were more susceptible to infection than older ones, regardless of host or parasite clone. Also, younger-infected D. magna became castrated faster than older hosts, but host and parasite clone effects contributed to this trait as well. Furthermore, the early-infected D. magna produced considerably more parasite transmission stages than late-infected ones, while host age at exposure did not affect virulence as it is defined in models (host mortality). When virulence is defined more broadly as the negative effects of infection on host fitness, by integrating the parasitic effects on host fecundity and mortality, then host age at exposure seems to slide along a negative relationship between host and parasite fitness. Thus, the virulence-transmission trade-off differs strongly among age classes, which in turn affects predictions of optimal virulence. Age-dependent effects on host susceptibility, virulence and parasite transmission could pose an important challenge for experimental and theoretical studies of infectious disease dynamics and disease ecology. Our results present a call for a more explicit stage-structured theory for disease, which will incorporate age-dependent epidemiological parameters. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Host social behavior and parasitic infection: A multifactorial approach

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Ezenwa, V.O.

2004-01-01

I examined associations between several components of host social organization, including group size and gregariousness, group stability, territoriality and social class, and gastrointestinal parasite load in African bovids. At an intraspecific level, group size was positively correlated with parasite prevalence, but only when the parasite was relatively host specific and only among host species living in stable groups. Social class was also an important predictor of infection rates. Among gazelles, territorial males had higher parasite intensities than did either bachelor males or females and juveniles, suggesting that highly territorial individuals may be either more exposed or more susceptible to parasites. Associations among territoriality, grouping, and parasitism were also found across taxa. Territorial host genera were more likely to be infected with strongyle nematodes than were nonterritorial hosts, and gregarious hosts were more infected than were solitary hosts. Analyses also revealed that gregariousness and territoriality had an interactive effect on individual parasite richness, whereby hosts with both traits harbored significantly more parasite groups than did hosts with only one or neither trait. Overall, study results indicate that multiple features of host social behavior influence infection risk and suggest that synergism between traits also has important effects on host parasite load.

Breastfeeding and risk of parasitic infection-a review

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Prameela Kannan Kutty

2014-11-01

Full Text Available Breastfeeding, as exclusive nutrition in the first six months of life, is a necessary nutritional requisite in infants. Except for very few maternal diseases that contraindicate breastfeeding, some of which still controversial, breastfeeding mothers must continue exclusive and sustained lactation to provide maximum overall benefits through breastfeeding. Parasitic infections is a global disease and children remain a significant proportion of the affected population. The complex and mandatory life cycles of some parasites, particularly the helminths may partly explain their geographical distribution. The world-wide prevalence of parasitic infections as well as the largely asymptomatic nature of most infections, make many of these infections to likely remain under-recognized. Breast milk, the prime infant nutrition must be recognized to be more than a rare vehicle of parasite transmission, but also a general and focused immune defensive tool against some important parasites. The possibility and influence of small quantities of parasite antigens in breast milk have not been adequately explored. It is believed that useful immunological responses both direct and indirect in breast milk that occur due to the presence of parasite antigens, must be further studied in the light of both immediate and long term benefits. Within this context, and prompted by a spectrum of existing uncertainties, researched and hypothetical roles of parasites and associated immunological responses in the lactating mammary gland are proposed and reviewed.

Intestinal parasitic infections in HIV-infected patients, Lao People's Democratic Republic.

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Phimpha Paboriboune

Full Text Available BACKGROUND: HIV infection is an emerging problem in Laos. We conducted the first prospective study on intestinal parasites, including opportunistic protozoa, in newly diagnosed HIV infected patients, with or without diarrhea. The aims were to describe the spectrum of infections, to determine their prevalence and to assess their associations with diarrhea, CD4 cell count, place of residence and living conditions. METHODOLOGY: One to three stool samples over consecutive days were obtained from 137 patients. The Kato thick smear method, formalin-ethyl concentration and specific stains for coccidia and microsporidia diagnosis were performed on 260 stool samples. Baseline characteristics regarding relevant demographics, place of residence and living conditions, clinical features including diarrhea, were collected using a standardized questionnaire. PRINCIPAL FINDINGS: The 137 patients were young (median age: 36 years and severely immunocompromised (83.9% at WHO stage 3 or 4, median CD4 cell count: 41/mm3. Diarrhea was present in 43.0% of patients. Parasite infection was found in 78.8% of patients, infection with at least two species in 49.6%. Prevalence rates of protozoan and helminth infections were similar (54.7% and 58.4% respectively. Blastocystis sp. was the most frequent protozoa (26.3%. Cryptosporidium sp., Cytoisospora belli and microsporidia, found at low prevalence rates (6.6%, 4.4%, 2.9%, respectively, were described for the first time in Laos. Cryptosporidium sp. was associated with persistent diarrhea. Strongyloides stercoralis was the most prevalent helminth following Opisthorchis viverrini (20.4% and 47.5% respectively. The most immunocompromised patients, as assessed by a CD4 count ≤ 50 cells/mm3, were more likely to be infected with intestinal parasites. CONCLUSIONS/SIGNIFICANCE: HIV infection was mainly diagnosed at an advanced stage of immunosuppression in Lao patients. Intestinal parasite infections were highly prevalent

Neutrophil and Alveolar Macrophage-Mediated Innate Immune Control of Legionella pneumophila Lung Infection via TNF and ROS.

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Pascal Ziltener

2016-04-01

Full Text Available Legionella pneumophila is a facultative intracellular bacterium that lives in aquatic environments where it parasitizes amoeba. However, upon inhalation of contaminated aerosols it can infect and replicate in human alveolar macrophages, which can result in Legionnaires' disease, a severe form of pneumonia. Upon experimental airway infection of mice, L. pneumophila is rapidly controlled by innate immune mechanisms. Here we identified, on a cell-type specific level, the key innate effector functions responsible for rapid control of infection. In addition to the well-characterized NLRC4-NAIP5 flagellin recognition pathway, tumor necrosis factor (TNF and reactive oxygen species (ROS are also essential for effective innate immune control of L. pneumophila. While ROS are essential for the bactericidal activity of neutrophils, alveolar macrophages (AM rely on neutrophil and monocyte-derived TNF signaling via TNFR1 to restrict bacterial replication. This TNF-mediated antibacterial mechanism depends on the acidification of lysosomes and their fusion with L. pneumophila containing vacuoles (LCVs, as well as caspases with a minor contribution from cysteine-type cathepsins or calpains, and is independent of NLRC4, caspase-1, caspase-11 and NOX2. This study highlights the differential utilization of innate effector pathways to curtail intracellular bacterial replication in specific host cells upon L. pneumophila airway infection.

Arginine and Polyamines Fate in Leishmania Infection

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Muxel, Sandra M.; Aoki, Juliana I.; Fernandes, Juliane C. R.; Laranjeira-Silva, Maria F.; Zampieri, Ricardo A.; Acuña, Stephanie M.; Müller, Karl E.; Vanderlinde, Rubia H.; Floeter-Winter, Lucile M.

2018-01-01

Leishmania is a protozoan parasite that alternates its life cycle between the sand fly and the mammalian host macrophages, involving several environmental changes. The parasite responds to these changes by promoting a rapid metabolic adaptation through cellular signaling modifications that lead to transcriptional and post-transcriptional gene expression regulation and morphological modifications. Molecular approaches such as gene expression regulation, next-generation sequencing (NGS), microRNA (miRNA) expression profiling, in cell Western blot analyses and enzymatic activity profiling, have been used to characterize the infection of murine BALB/c and C57BL/6 macrophages, as well as the human monocytic cell-lineage THP-1, with Leishmania amazonensis wild type (La-WT) or arginase knockout (La-arg-). These models are being used to elucidate physiological roles of arginine and polyamines pathways and the importance of arginase for the establishment of the infection. In this review, we will describe the main aspects of Leishmania-host interaction, focusing on the arginine and polyamines pathways and pointing to possible targets to be used for prognosis and/or in the control of the infection. The parasite enzymes, arginase and nitric oxide synthase-like, have essential roles in the parasite survival and in the maintenance of infection. On the other hand, in mammalian macrophages, defense mechanisms are activated inducing alterations in the mRNA, miRNA and enzymatic profiles that lead to the control of infection. Furthermore, the genetic background of both parasite and host are also important to define the fate of infection. PMID:29379478

Gastrointestinal parasite infection of the Gray mouse lemur ...

African Journals Online (AJOL)

Faecal material from 169 individuals of Microcebus murinus living in five littoral forest fragments was analyzed for gastrointestinal parasites. The fragments differed in size and forest quality. Gastrointestinal parasite infection of M. murinus was characterised using parasite species richness, the prevalence of parasites, and ...

Parasite infection alters nitrogen cycling at the ecosystem scale.

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Mischler, John; Johnson, Pieter T J; McKenzie, Valerie J; Townsend, Alan R

2016-05-01

Despite growing evidence that parasites often alter nutrient flows through their hosts and can comprise a substantial amount of biomass in many systems, whether endemic parasites influence ecosystem nutrient cycling, and which nutrient pathways may be important, remains conjectural. A framework to evaluate how endemic parasites alter nutrient cycling across varied ecosystems requires an understanding of the following: (i) parasite effects on host nutrient excretion; (ii) ecosystem nutrient limitation; (iii) effects of parasite abundance, host density, host functional role and host excretion rate on nutrient flows; and (iv) how this infection-induced nutrient flux compares to other pools and fluxes. Pathogens that significantly increase the availability of a limiting nutrient within an ecosystem should produce a measurable ecosystem-scale response. Here, we combined field-derived estimates of trematode parasite infections in aquatic snails with measurements of snail excretion and tissue stoichiometry to show that parasites are capable of altering nutrient excretion in their intermediate host snails (dominant grazers). We integrated laboratory measurements of host nitrogen excretion with field-based estimates of infection in an ecosystem model and compared these fluxes to other pools and fluxes of nitrogen as measured in the field. Eighteen nitrogen-limited ponds were examined to determine whether infection had a measurable effect on ecosystem-scale nitrogen cycling. Because of their low nitrogen content and high demand for host carbon, parasites accelerated the rate at which infected hosts excreted nitrogen to the water column in a dose-response manner, thereby shifting nutrient stoichiometry and availability at the ecosystem scale. Infection-enhanced fluxes of dissolved inorganic nitrogen were similar to other commonly important environmental sources of bioavailable nitrogen to the system. Additional field measurements within nitrogen-limited ponds indicated that

Parasite Infection, Carcinogenesis and Human Malignancy

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Hoang van Tong

2017-02-01

Full Text Available Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

Parasite Infection, Carcinogenesis and Human Malignancy.

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van Tong, Hoang; Brindley, Paul J; Meyer, Christian G; Velavan, Thirumalaisamy P

2017-02-01

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

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Sonali Singh

Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF, on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1 and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human

Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

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Singh, Sonali; Barr, Helen; Liu, Yi-Chia; Robins, Adrian; Heeb, Stephan; Williams, Paul; Fogarty, Andrew; Cámara, Miguel; Martínez-Pomares, Luisa

2015-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages

Parasitic infections of amphibians in the Pendjari Biosphere ...

African Journals Online (AJOL)

Parasitic infections of amphibians in the Pendjari Biosphere Reserve, Benin. ... Results obtained show the possible influence of land-use pattern on parasite distribution. For example, the ... Furthermore, this infection pattern may be indicative of an immunosuppressive effect of pesticides on the frogs of the Agricultural Zone.

Toxoplasma gondii exposes phosphatidylserine inducing a TGF-β1 autocrine effect orchestrating macrophage evasion

International Nuclear Information System (INIS)

Seabra, Sergio H.; Souza, Wanderley de; Matta, Renato A. da

2004-01-01

Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO production persisting in activated macrophages depends on phosphatidylserine (PS) exposure. Masking PS with annexin-V on parasites or activated macrophages abolished NO production inhibition and parasite persistence. NO production inhibition depended on a transforming growth factor-β 1 (TGF-β 1 ) autocrine effect confirmed by the expression of Smad 2 and 3 in infected macrophages. TGF-β 1 led to inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin) depolymerization, and lack of nuclear factor-κB (NF-κB) in the nucleus. All these features were reverted by TGF-β 1 neutralizing antibody treatment. Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and also the anti-inflammatory response evoked by apoptotic cells

Intestinal parasitic infection among school children.

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Shakya, B; Shrestha, S; Madhikarmi, N L; Adhikari, R

2012-01-01

Intestinal parasitosis is a major public health problem of developing countries, children being major victims. Higher prevalence has been reported among school children, mostly in hilly regions of Nepal. This study aims at assessing prevalence of intestinal parasitosis among school children of a school in a border town of Nepal and the associated factors. Fecal samples from the students were examined by direct smear technique and result was correlated with their socioeconomic status and hygienic behavior. The chi-square test was used for analytical assessment. The prevalence rate was 13.9%, girls being highly infected (19.1%) than boys (10.3%) (P>0.05). Entamoeba histolytica (36.0%) was the commonest parasite followed by A. lumbricoides (28.0%). The highest positive rate was found among children of 5 years and less age (29.2%) and least among those above 12 years (5.3%) (P>0.05). Those from family size 5 and less than 5 were least infected (10.5%). Children of illiterate parents (16.7%) and farmers (17.1%) were more infected than literate ones and non-farmers (P>0.05). 8.7% of positive children had multi-parasitic infection. Children drinking untreated water (15.0%) were more infected than those drinking treated water (5.5%) (P>0.05). Intestinal parasitic infection was found among 17% school children. Awareness on infectious diseases, improving hygiene, and application of supportive programs for parents to elevate socioeconomic conditions may reduce the burden of infection.

PARASITIC INFECTIONS OF DRY SEASON FARMERS IN SOME ...

African Journals Online (AJOL)

Standard laboratory procedures were adopted in the collection, processing and parasite identification in the stool samples. The rates of parasites infections in the farmers were 91.6% for helminthes and 86.4% for protozoa. Helminth infection rates but not those of protozoa, varied significantly between farmers and controls.

Effect of influenza infection on the phagocytic and bactericidal activities of pulmonary macrophages

International Nuclear Information System (INIS)

Nugent, K.M.; Pesanti, E.L.

1979-01-01

The effect of mouse-adapted influenza A/PR/8/34 virus on pulmonary macrophage function was evaluated by using an in vitro system which allowed direct virus interaction with macrophages and then separate analysis of the steps required for bacterial clearance by macrophages. Infection of macrophages with this virus resulted in the appearance of a hemagglutinating activity on the macrophage surface; expression of this activity was inhibited by amantadine, 2-deoxyglucose, and cycloheximide and by pretreatment of the virus inoculum with with ultraviolet light and specific antiserum. After influenza infection, net ingestion of viable Staphylococcus aureus by macrophage monolayers was unaltered and there was no change in the fraction of the monolayer which ingested cocci over a wide range of bacterial inputs. Influenza-infected microphages also inactivated intracellular S. aureus at a rate indistinguishable from controls. Therefore, these in vitro studies do not support the hypothesis that the defect in pulmonary antibacterial mechanisms associated with influenza infections results from a direct effect of virus infection on either the phagocytic or bactericidal activity of resistant pulmonary macarophages

TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages.

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Takano, Tomomi; Hohdatsu, Tsutomu; Toda, Ayako; Tanabe, Maki; Koyama, Hiroyuki

2007-07-20

The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.

The risk of pathogenic intestinal parasite infections in Kisii Municipality, Kenya

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Kabiru Ephantus W

2008-07-01

Full Text Available Abstract Background Intestinal parasitic infections are among the most common infections worldwide. Various epidemiological studies indicate that the prevalence of intestinal parasites is high especially in developing countries, although in many of these, the environmental risk factors have not been clearly elucidated. The objective of this study was to determine the risk of pathogenic intestinal parasites infections in Kisii Municipality. Methods Random sampling was used in the selection of the study samples. Stool parasitological profiles of food handlers were done by direct smear and formalin-ethyl acetate sedimentation method. Both vegetable and meat samples were examined for the presence of intestinal parasites. The storage and meat handling practices of the various butcheries were observed. Results Types of samples examined for occurrence of intestinal parasites includes, a total of 84 vegetable, 440 meat and 168 stool samples. Fifty five (65.5% vegetable, 334 (75.9% meat and 69 (41.1% of the stool samples were found positive for intestinal parasites indicating a high overall risk (66.18% for intestinal parasite infections. Of the parasites detected, the most common parasites infesting the foodstuffs and infecting the food handlers were Ascaris lumbricoides and Entamoeba histolytica. Parasites were significantly less likely to be present on meat that was refrigerated during display than meat that was displayed at ambient temperature. Conclusion There is a high risk of infection with intestinal parasites in the sampled Municipal markets. About half of the food handlers surveyed (41.1 % at the Municipal Hospital had one or more parasitic infections. Furthermore, meat (65.5% and vegetables (75.9% sold at the Municipal market were found to be contaminated with parasites hence the inhabitants requires a need for education on food safety, good distribution practices and improvement on sanitary conditions.

The double edge to parasite escape: invasive host is less infected but more infectable.

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Keogh, Carolyn L; Miura, Osamu; Nishimura, Tomohiro; Byers, James E

2017-09-01

Nonnative species that escape their native-range parasites may benefit not only from reduced infection pathology, but also from relaxed selection on costly immune defenses, promoting reallocation of resources toward growth or reproduction. However, benefits accruing from a reduction in defense could come at the cost of increased infection susceptibility. We conducted common garden studies of the shore crab Hemigrapsus sanguineus from highly parasitized native (Japan) populations and largely parasite-free invasive (USA) populations to test for differences in susceptibility to infection by native-range rhizocephalan parasites, and to explore differences in host resource allocation. Nonnative individuals showed at least 1.8 times greater susceptibility to infection than their native counterparts, and had reduced standing metabolic rates, suggesting that less of their energy was spent on physiological self-maintenance. Our results support an indirect advantage to parasite escape via the relaxation of costly physiological defenses. However, this advantage comes at the cost of heightened susceptibility, a trade-off of parasite escape that is seldom considered. © 2017 by the Ecological Society of America.

The utility of screening for parasitic infections in HIV-1-infected Africans with eosinophilia in London.

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Sarner, Liat; Fakoya, Ade O; Tawana, Cheryl; Allen, Elizabeth; Copas, Andrew J; Chiodini, Peter L; Fenton, Kevin A

2007-09-01

The presence of asymptomatic eosinophilia in HIV patients has been demonstrated to have a wide variety of causes. Untreated parasitic infections in immunocompromised individuals can have potentially serious consequences. The utility of screening for parasitic infections in immigrant HIV-positive Africans with eosinophilia was investigated in a UK-based HIV clinic. HIV-positive African patients with eosinophilia were matched with HIV-positive African controls without eosinophilia. More than half of African HIV patients with eosinophilia had positive parasitic serology, and were significantly more likely to have positive serology compared with African HIV patients without eosinophilia. This study shows that asymptomatic eosinophilia in HIV-1-infected Africans is strongly suggestive of underlying parasitic infection. Individuals with eosinophilia should thus be screened for parasitic infections according to the infections prevalent in the countries they have lived in or visited for substantial periods of time.

Sex steroids, immune system, and parasitic infections: facts and hypotheses.

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Nava-Castro, Karen; Hernández-Bello, Romel; Muñiz-Hernández, Saé; Camacho-Arroyo, Ignacio; Morales-Montor, Jorge

2012-07-01

It has been widely reported that the incidence and the severity of natural parasitic infections are different between males and females of several species, including humans. This sexual dimorphism involves a distinct exposure of males and females to various parasite infective stages, differential effects of sex steroids on immune cells, and direct effects of these steroids on parasites, among others. Typically, for a large number of parasitic diseases, the prevalence and intensity is higher in males than females; however, in several parasitic infections, males are more resistant than females. In the present work, we review the effects of sex hormones on immunity to protozoa and helminth parasites, which are the causal agents of several diseases in humans, and discuss the most recent research related to the role of sex steroids in the complex host-parasite relationship. © 2012 New York Academy of Sciences.

The Macrophage-Specific Promoter mfap4 Allows Live, Long-Term Analysis of Macrophage Behavior during Mycobacterial Infection in Zebrafish.

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Eric M Walton

Full Text Available Transgenic labeling of innate immune cell lineages within the larval zebrafish allows for real-time, in vivo analyses of microbial pathogenesis within a vertebrate host. To date, labeling of zebrafish macrophages has been relatively limited, with the most specific expression coming from the mpeg1 promoter. However, mpeg1 transcription at both endogenous and transgenic loci becomes attenuated in the presence of intracellular pathogens, including Salmonella typhimurium and Mycobacterium marinum. Here, we describe mfap4 as a macrophage-specific promoter capable of producing transgenic lines in which transgene expression within larval macrophages remains stable throughout several days of infection. Additionally, we have developed a novel macrophage-specific Cre transgenic line under the control of mfap4, enabling macrophage-specific expression using existing floxed transgenic lines. These tools enrich the repertoire of transgenic lines and promoters available for studying zebrafish macrophage dynamics during infection and inflammation and add flexibility to the design of future macrophage-specific transgenic lines.

ABO Blood Groups Influence Macrophage-mediated Phagocytosis of Plasmodium falciparum-infected Erythrocytes

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Branch, Donald R.; Hult, Annika K.; Olsson, Martin L.; Liles, W. Conrad; Cserti-Gazdewich, Christine M.; Kain, Kevin C.

2012-01-01

Erythrocyte polymorphisms associated with a survival advantage to Plasmodium falciparum infection have undergone positive selection. There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection. Based on the hypothesis that enhanced innate clearance of infected polymorphic erythrocytes is associated with protection from severe malaria, we investigated whether P. falciparum-infected O erythrocytes are more efficiently cleared by macrophages than infected A and B erythrocytes. We show that human macrophages in vitro and mouse monocytes in vivo phagocytose P. falciparum-infected O erythrocytes more avidly than infected A and B erythrocytes and that uptake is associated with increased hemichrome deposition and high molecular weight band 3 aggregates in infected O erythrocytes. Using infected A1, A2, and O erythrocytes, we demonstrate an inverse association of phagocytic capacity with the amount of A antigen on the surface of infected erythrocytes. Finally, we report that enzymatic conversion of B erythrocytes to type as O before infection significantly enhances their uptake by macrophages to observed level comparable to that with infected O wild-type erythrocytes. These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria. PMID:23071435

Prevalence of Intestinal Parasitic Infection among Food Handlers in Northwest Iran

Directory of Open Access Journals (Sweden)

Davoud Balarak

2016-01-01

Full Text Available Parasitic diseases are among the most important infectious diseases and pose health problems in many countries, most especially in developing countries. Workers at food centers could transmit parasitic infections in the absence of sanitation. This is a descriptive study conducted to determine the prevalence of intestinal parasitic infections in food clerks in the city of Tabriz in 2014. Data was recorded in the offices of the health center for all food handlers who were referred to the laboratory for demographic and stool tests to receive the health card. Parasitic infection was observed in 172 cases (3.73% of 4612 samples. A total of 156 positive samples (90.69% were related to protozoa and 16 (9.3% were related to helminthes. Most of the parasitic infections were related to Giardia and Entamoeba coli and the lowest infection was related to H. nana. Also, there was a significant relationship between level of education and parasitic infection rate (P=0.0044. But there was no significant difference between the type of infection and amount of intestinal parasites. The results show that the prevalence of intestinal parasites, especially pathogenic protozoa, is common in some food handlers. Therefore, more sanitary controls are required and increasing of education will play a crucial role in improving the health of these people.

Inhibition of ecto-ATPase activities impairs HIV-1 infection of macrophages.

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Schachter, Julieta; Delgado, Kelly Valcárcel; Barreto-de-Souza, Victor; Bou-Habib, Dumith Chequer; Persechini, Pedro Muanis; Meyer-Fernandes, José Roberto

2015-05-01

Nucleotides and nucleosides are secreted into extracellular media at different concentrations as a consequence of different physiologic and pathological conditions. Ecto-nucleotidases, enzymes present on the surface of most cells, hydrolyze these extracellular nucleotides and reduce the concentration of them, thus affecting the activation of different nucleotide and nucleoside receptors. Also, ecto-nucleotidases are present in a number of microorganisms and play important roles in host-pathogen interactions. Here, we characterized the ecto-ATPase activities present on the surface of HIV-1 particle and human macrophages as well. We found that the kinetic properties of HIV-1 and macrophage ecto-ATPases are similar, suggesting that the enzyme is the same. This ecto-ATPase activity was increased in macrophages infected in vitro with HIV-1. Using three different non-related ecto-ATPase inhibitors-POM-1, ARL67156 and BG0-we showed that the inhibition of these macrophage and viral ecto-ATPase activities impairs HIV-1 infection. In addition, we also found that elevated extracellular concentrations of ATP inhibit HIV-1 production by infected macrophages. Copyright © 2014 Elsevier GmbH. All rights reserved.

Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

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Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

2010-01-01

Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

Proteomic Investigation of the Time Course Responses of RAW 264.7 Macrophages to Infection with Salmonella enterica

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Shi, Liang; Chowdhury, Saiful M.; Smallwood, Heather S.; Yoon, Hyunjin; Mottaz-Brewer, Heather M.; Norbeck, Angela D.; McDermott, Jason E.; Clauss, Therese RW; Heffron, Fred; Smith, Richard D.; Adkins, Joshua N.

2009-08-01

Macrophages plan important roles in controlling Salmonella-mediated systemic infection. To investigate the responses of macrophages to Salmonella infection, we infected RAW 264.7 macrophages with Salmonella enterica serovar Typhimurium (STM) and then performed a comparative liquid chromatography-tandem mass spectrometry [LC-MS(/MS)]-based proteomics analysis of the infected macrophages. A total of 1006 macrophage and 115 STM proteins were indentified from this study. Most of STM proteins were found at late stage of the time course of infection, consistent with the fact that STM proliferates inside RAW 264.7 macrophages. Majority of the identified macrophage proteins were house keeping-related, including cytoplasmic superoxide dismutase 1 (SOD1), whose peptide abundances were relatively constant during the time course of infection. Compared to those in no infection control, the peptide abundances of 244 macrophage proteins (or 24% of total indentified macrophage proteins) changed considerably after STM infection. The functions of these STM infection-affected macrophage proteins were diverse and ranged from production of antibacterial nitric oxide (i.e., inducible nitric oxide synthase or iNOS) or production of prostaglandin H2 (i.e., prostaglandin-endoperoxide synthase 2, also know as cyclooxygenase-2 or COX-2) to regulation of intracellular traffic (e.g., sorting nexin or SNX 5, 6 and 9), demonstrating a global impact of STM infection on macrophage proteome. Western-blot analysis not only confirmed the LC-MS(/MS) results of SOD1, COX-2 and iNOS, but also revealed that the protein abundances of mitochondrial SOD2 increased after STM infection, indicating an infection-induced oxidative stress in mitochondria.

HIV-1-infected macrophages induce astrogliosis by SDF-1α and matrix metalloproteinases

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Okamoto, Mika; Wang, Xin; Baba, Masanori

2005-01-01

Brain macrophages/microglia and astrocytes are known to be involved in the pathogenesis of HIV-1-associated dementia (HAD). To clarify their interaction and contribution to the pathogenesis, HIV-1-infected or uninfected macrophages were used as a model of brain macrophages/microglia, and their effects on human astrocytes in vitro were examined. The culture supernatants of HIV-1-infected or uninfected macrophages induced significant astrocyte proliferation, which was annihilated with a neutralizing antibody to stromal cell-derived factor (SDF)-1α or a matrix metalloproteinase (MMP) inhibitor. In these astrocytes, CXCR4, MMP, and tissue inhibitors of matrix metalloproteinase mRNA expression and SDF-1α production were significantly up-regulated. The supernatants of infected macrophages were always more effective than those of uninfected cells. Moreover, the enhanced production of SDF-1α was suppressed by the MMP inhibitor. These results indicate that the activated and HIV-1-infected macrophages can indirectly induce astrocyte proliferation through up-regulating SDF-1α and MMP production, which implies a mechanism of astrogliosis in HAD

Enteric parasitic infections in HIV-infected patients with low CD4 counts in Toto, Nigeria

International Nuclear Information System (INIS)

Abaver, D.T.; Nwobegahay, J.M.; Goon, D.T.; Khoza, L.B

2012-01-01

Objectives: Enteric parasites are a major cause of diarrhoea in HIV/AIDS patients with low CD4 counts. Parasitic infections in HIV-infected individuals can reduce their quality of life and life span, especially those who are severely immunosuppressed with a CD4 T-lymphocyte count 0.05). Conclusions: Low CD4 counts in HIV-infected patients can lead to enteric infections. This information strengthens the importance of monitoring CD4 counts and intestinal parasites. Routine CD4 testing will greatly improve the prognosis of HIV positive patients. (author)

Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis.

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Sanches, Françoise P; Tomokane, Thaise Y; Da Matta, Vânia L R; Marcondes, Mary; Corbett, Carlos E P; Laurenti, Márcia D

2014-09-07

There are only a few studies reporting the role of nitric oxide metabolites for controlling macrophage intracellular parasitism, and these are controversial. Therefore, the present study aimed to evaluate the expression of inducible nitric oxide synthase (iNOS) in the lymph nodes and spleen of dogs affected by visceral leishmaniasis through immunohistochemistry and to determine its correlation with tissue parasite burden and serum interferon (IFN)-γ levels. Twenty-eight dogs were selected and assigned to one of two groups, symptomatic (n = 18) and asymptomatic (n = 10), according to clinical status and laboratory evaluation. A negative control group (n = 6) from a non-endemic region for visceral leishmaniasis was included as well. Parasite density (amastigotes/mm2) was similar between clinical groups in the lymph nodes (P = 0.2401) and spleen (P = 0.8869). The density of iNOS⁺ cells was higher in infected dogs compared to controls (P spleen (P = 0.5940) densities between symptomatic and asymptomatic dogs. A positive correlation was found between the number of iNOS⁺ cells in lymph nodes and interferon-γ levels (r = 0.3776; P = 0.0303), and there was a negative correlation between parasites and iNOS⁺ cell densities both in lymph nodes (r = -0.5341; P = 0.0034) and spleen (r = -0.4669; P = 0.0329). The negative correlation observed between tissue parasitism and the expression of iNOS may be a reflection of NO acting on the control of parasites.

Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection.

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Bai, Xiyuan; Oberley-Deegan, Rebecca E; Bai, An; Ovrutsky, Alida R; Kinney, William H; Weaver, Michael; Zhang, Gong; Honda, Jennifer R; Chan, Edward D

2016-07-01

With the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosis-an effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB). An in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival. We found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFκB) activation. Curcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development. © 2016 Asian Pacific Society of Respirology.

Prevalence of intestinal parasitic infections among patients ...

African Journals Online (AJOL)

Gastrointestinal helminths and protozoan parasites may cause mild, acute and chronic human infections. There is inadequate reliable information on the epidemiology of these parasites among patients attending tertiary hospitals in Tanzania. This retrospective study was conducted using hospital data obtained from the ...

Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

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Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

2013-01-01

The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

Epilepsy and tropical parasitic infections in Sub-Saharan Africa: a ...

African Journals Online (AJOL)

Saharan Africa is associated with the high prevalence of parasitic infections affecting the central nervous system. Though epidemiological evidence suggests an association between parasitic infections and epilepsy, the biological causal ...

Human parasitic protozoan infection to infertility: a systematic review.

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Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

2016-02-01

Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

Parasitic Infections among Restaurant Workers in Mukalla (Hadhramout/Yemen

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AM AL-Haddad

2008-09-01

Full Text Available "nBackground: To identify intestinal parasites among restaurant workers in Mukalla, Yemen in 2007."nMethods: Stool specimens were collected and examined from a total of 500 restaurant workers at Hadhramout University Health Center .Three types of techniques were used: direct examination, saline sedimentation and formol-ether concentration."nResults:  The positivity in majority of them was single infection whereas 6 cases were double infection that constituted 1.3% of the prevalence. The prevalence was 14.8 % for Entamoeba histolytica/dispor, and 5.2 % for Giardia lamblia, while it was 4.4% for Hymenolepis nana. Other intestinal parasites including Ascaris lumbricoides, Ancylostoma duodinale were also detected. Additionally, the blood parasite Schistosoma mansoni was also detected in 4 cases. The double infection was only with E. histolytica/dispor and Giardia. The infection with these parasites was also accompanied by abdominal troubles "diarrhea, constipation", nausea and vomiting."nConclusion:  These results lead to understand that sanitary measurements are not effective, and this hazardous situation facilitate parasitic agents' distribution among clients. The effectiveness of current pre-employment screening policy must be annual and systematic surveillance is needed in addition to health education.

Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

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Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

2017-08-15

A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV/SIV-infected

Intestinal Parasitic Infections in Primary School Children in Rural ...

African Journals Online (AJOL)

Background: Intestinal parasitic infections are a major public health problem in developing countries where majority of the affected persons are children. This study is aimed at determining the prevalence of intestinal parasitic infections and the effect of socio-demography in some rural primary schools in Ovia Northeast ...

Poliovirus and other enteroviruses in children infected with intestinal parasites in Nigeria.

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Adekolujo, Daniel R; Olayinka, Suraj O; Adeniji, Johnson A; Oyeyemi, Oyetunde T; Odaibo, Alexander B

2015-10-29

Poliovirus, an enterovirus, still persists in Nigeria despite the global efforts tailored towards its eradication. This study aimed to assess the impacts of poliovirus and other enteroviruses on the susceptibility of individuals to intestinal parasite infections. A cross-sectional study on the prevalence of intestinal parasites was conducted on two-sample stool specimens of 717 Nigerian children (between 1 and 19 years of age) whose poliovirus/other enteroviruses infection status had been determined. The overall prevalence of Sabin poliovirus and other related enteroviruses infections were 6.6% and 13.8%, respectively. The prevalence of Ascaris lumbricoides was significantly higher than that of other intestinal parasites (p parasitic infection (OR = 11.7, CI = 9.2-15.0). While the prevalence of all species of parasites except S. mansoni showed no significant variations in children with Sabin poliovirus (p > 0.05), the prevalence of hookworms and Taenia spp. was significantly higher in children with other enteroviral infections (p parasites is an indication of possible association of the parasites in a more poliovirus-endemic population. A combined intervention approach for the two infections is advocated.

l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis

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Abhishek Mandal

2017-07-01

Full Text Available The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL, depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important

Intestinal Parasitic Infections in HIV Infected and Non-Infected Patients in a Low HIV Prevalence Region, West-Cameroon

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Nkenfou, Céline Nguefeu; Nana, Christelle Tafou; Payne, Vincent Khan

2013-01-01

The magnitude of intestinal parasitic infection in acquired immunodeficiency syndrome patients requires careful consideration in the developing world where poor nutrition is associated with poor hygiene and several tropical diseases. However, there have been very few studies addressing this issue in Cameroon. This study was conducted to determine the prevalence of intestinal parasitosis in HIV/AIDS patients in Dschang -Cameroon. Stool and blood specimens from HIV/AIDS patients and control group were screened respectively for intestinal parasites and for HIV antibodies. Intestinal parasites were identified using direct microscopy, formalin-ether concentration and Ziehl Neelsen methods. Out of 396 participants recruited among patients consulting at hospital, 42 (10.6%) were HIV positive, thirty of them treatment naïve. The overall prevalence of intestinal parasites was 14.64%. Out of 42 HIV/AIDS patients, 59.5% (25/42) were infected with intestinal parasites, while only 9.32% (33/354) of the HIV negative patients were infected with intestinal parasites. The parasites detected in our study population included Crystosporidium parvum (2.53%), Entamoeba histolytica (7.52%), Entamoeba coli (4.04%), Giardia lamblia (0.25%), Trichuris trichura (0.25%), Strongyloides stercoralis (0.25%) and Taenia spp. (0.25%). In the HIV infected group, Crystosporidium parvum (19.04%), Entamoeba histolytica (19.04%), Entamoeba coli (21.42%), Giardia lamblia (2.38%), Strongyloides stercoralis (0.25%) and Taenia spp. (0.25%) were found. Crystosporidium parvum was found to be significantly higher in HIV/AIDS patients than in controls (Pintestinal parasitosis. Routine examinations of stool samples for parasites would significantly benefit the HIV patients by contributing in reducing morbidity and improving the efficiency of antiretroviral treatment. Even after the introduction of free anti-retroviral drugs, opportunistic intestinal infections are still a threat. HIV patients should be screened

Experimental Infection and Clearance of Coccidian Parasites in Mercury-Exposed Zebra Finches.

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Ebers Smith, Jessica H; Cristol, Daniel A; Swaddle, John P

2018-01-01

Mercury is a globally distributed, persistent environmental contaminant that affects the health of many taxa. It can suppress the immune system, which often plays a role in defense against parasites. However, there have been few investigations of whether mercury affects the abilities of animals to resist parasitic infection. Here, we exposed zebra finches to a lifetime dietary exposure of methylmercury (1.2 μg/g wet weight) and experimentally infected them with coccidian parasites to examine the effect of methylmercury exposure on parasitic infection. The mercury-exposed birds did not have an altered immune response (heterophil:lymphocyte ratio) nor a reduced ability to clear the infection. However, mercury-exposed birds tended to have higher parasite loads at the time when we expected the greatest immune response (2-3 weeks post-infection). Although mercury did not greatly influence the infection-course of this parasite in captivity, responses may be more accentuated in the wild where birds face additional immune challenges.

Essential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages.

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Tanigawa, Kazunari; Degang, Yang; Kawashima, Akira; Akama, Takeshi; Yoshihara, Aya; Ishido, Yuko; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

2012-05-01

Mycobacterium leprae (M. leprae), the causative agent of leprosy, parasitizes within the foamy or enlarged phagosome of macrophages where rich lipids accumulate. Although the mechanisms for lipid accumulation in the phagosome have been clarified, it is still unclear how such large amounts of lipids escape degradation. To further explore underlying mechanisms involved in lipid catabolism in M. leprae-infected host cells, we examined the expression of hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization and lipolysis, in human macrophage THP-1 cells. We found that infection by live M. leprae significantly suppressed HSL expression levels. This suppression was not observed with dead M. leprae or latex beads. Macrophage activation by peptidoglycan (PGN), the ligand for toll-like receptor 2 (TLR2), increased HSL expression; however, live M. leprae suppressed this increase. HSL expression was abolished in the slit-skin smear specimens from patients with lepromatous and borderline leprosy. In addition, the recovery of HSL expression was observed in patients who experienced a lepra reaction, which is a cell-mediated, delayed-type hypersensitivity immune response, or in patients who were successfully treated with multi-drug therapy. These results suggest that M. leprae suppresses lipid degradation through inhibition of HSL expression, and that the monitoring of HSL mRNA levels in slit-skin smear specimens may be a useful indicator of patient prognosis.

Real-time visualization of HIV-1 GAG trafficking in infected macrophages.

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Karine Gousset

2008-03-01

Full Text Available HIV-1 particle production is driven by the Gag precursor protein Pr55(Gag. Despite significant progress in defining both the viral and cellular determinants of HIV-1 assembly and release, the trafficking pathway used by Gag to reach its site of assembly in the infected cell remains to be elucidated. The Gag trafficking itinerary in primary monocyte-derived macrophages is especially poorly understood. To define the site of assembly and characterize the Gag trafficking pathway in this physiologically relevant cell type, we have made use of the biarsenical-tetracysteine system. A small tetracysteine tag was introduced near the C-terminus of the matrix domain of Gag. The insertion of the tag at this position did not interfere with Gag trafficking, virus assembly or release, particle infectivity, or the kinetics of virus replication. By using this in vivo detection system to visualize Gag trafficking in living macrophages, Gag was observed to accumulate both at the plasma membrane and in an apparently internal compartment that bears markers characteristic of late endosomes or multivesicular bodies. Significantly, the internal Gag rapidly translocated to the junction between the infected macrophages and uninfected T cells following macrophage/T-cell synapse formation. These data indicate that a population of Gag in infected macrophages remains sequestered internally and is presented to uninfected target cells at a virological synapse.

Leishmania infantum ecto-nucleoside triphosphate diphosphohydrolase-2 is an apyrase involved in macrophage infection and expressed in infected dogs.

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Raphael De Souza Vasconcellos

2014-11-01

Full Text Available Visceral leishmaniasis is an important tropical disease, and Leishmania infantum chagasi (synonym of Leishmania infantum is the main pathogenic agent of visceral leishmaniasis in the New World. Recently, ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases were identified as enablers of infection and virulence factors in many pathogens. Two putative E-NTPDases (∼70 kDa and ∼45 kDa have been found in the L. infantum genome. Here, we studied the ∼45 kDa E-NTPDase from L. infantum chagasi to describe its natural occurrence, biochemical characteristics and influence on macrophage infection.We used live L. infantum chagasi to demonstrate its natural ecto-nucleotidase activity. We then isolated, cloned and expressed recombinant rLicNTPDase-2 in bacterial system. The recombinant rLicNTPDase-2 hydrolyzed a wide variety of triphosphate and diphosphate nucleotides (GTP> GDP  =  UDP> ADP> UTP  =  ATP in the presence of calcium or magnesium. In addition, rLicNTPDase-2 showed stable activity over a pH range of 6.0 to 9.0 and was partially inhibited by ARL67156 and suramin. Microscopic analyses revealed the presence of this protein on cell surfaces, vesicles, flagellae, flagellar pockets, kinetoplasts, mitochondria and nuclei. The blockade of E-NTPDases using antibodies and competition led to lower levels of parasite adhesion and infection of macrophages. Furthermore, immunohistochemistry showed the expression of E-NTPDases in amastigotes in the lymph nodes of naturally infected dogs from an area of endemic visceral leishmaniasis.In this work, we cloned, expressed and characterized the NTPDase-2 from L. infantum chagasi and demonstrated that it functions as a genuine enzyme from the E-NTPDase/CD39 family. We showed that E-NTPDases are present on the surface of promastigotes and in other intracellular locations. We showed, for the first time, the broad expression of LicNTPDases in naturally infected dogs. Additionally, the blockade of

Leishmania infantum Ecto-Nucleoside Triphosphate Diphosphohydrolase-2 is an Apyrase Involved in Macrophage Infection and Expressed in Infected Dogs

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Vasconcellos, Raphael De Souza; Mariotini-Moura, Christiane; Gomes, Rodrigo Saar; Serafim, Tiago Donatelli; Firmino, Rafaela de Cássia; Silva e Bastos, Matheus; de Castro, Felipe Freitas; de Oliveira, Claudia Miranda; Borges-Pereira, Lucas; de Souza, Anna Cláudia Alves; de Souza, Ronny Francisco; Gómez, Gabriel Andres Tafur; Pinheiro, Aimara da Costa; Maciel, Talles Eduardo Ferreira; Silva-Júnior, Abelardo; Bressan, Gustavo Costa; Almeida, Márcia Rogéria; Baqui, Munira Muhammad Abdel; Afonso, Luís Carlos Crocco; Fietto, Juliana Lopes Rangel

2014-01-01

Background Visceral leishmaniasis is an important tropical disease, and Leishmania infantum chagasi (synonym of Leishmania infantum) is the main pathogenic agent of visceral leishmaniasis in the New World. Recently, ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) were identified as enablers of infection and virulence factors in many pathogens. Two putative E-NTPDases (∼70 kDa and ∼45 kDa) have been found in the L. infantum genome. Here, we studied the ∼45 kDa E-NTPDase from L. infantum chagasi to describe its natural occurrence, biochemical characteristics and influence on macrophage infection. Methodology/Principal Findings We used live L. infantum chagasi to demonstrate its natural ecto-nucleotidase activity. We then isolated, cloned and expressed recombinant rLicNTPDase-2 in bacterial system. The recombinant rLicNTPDase-2 hydrolyzed a wide variety of triphosphate and diphosphate nucleotides (GTP> GDP  =  UDP> ADP> UTP  =  ATP) in the presence of calcium or magnesium. In addition, rLicNTPDase-2 showed stable activity over a pH range of 6.0 to 9.0 and was partially inhibited by ARL67156 and suramin. Microscopic analyses revealed the presence of this protein on cell surfaces, vesicles, flagellae, flagellar pockets, kinetoplasts, mitochondria and nuclei. The blockade of E-NTPDases using antibodies and competition led to lower levels of parasite adhesion and infection of macrophages. Furthermore, immunohistochemistry showed the expression of E-NTPDases in amastigotes in the lymph nodes of naturally infected dogs from an area of endemic visceral leishmaniasis. Conclusions/Significance In this work, we cloned, expressed and characterized the NTPDase-2 from L. infantum chagasi and demonstrated that it functions as a genuine enzyme from the E-NTPDase/CD39 family. We showed that E-NTPDases are present on the surface of promastigotes and in other intracellular locations. We showed, for the first time, the broad expression of LicNTPDases in

Eosinophilic fasciitis after parasite infection

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Marta Oliveira

2016-03-01

Full Text Available Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer.

Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP.

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Kishore V L Parsa

2006-07-01

Full Text Available Francisella tularensis, a Gram-negative facultative intracellular pathogen infecting principally macrophages and monocytes, is the etiological agent of tularemia. Macrophage responses to F. tularensis infection include the production of pro-inflammatory cytokines such as interleukin (IL-12, which is critical for immunity against infection. Molecular mechanisms regulating production of these inflammatory mediators are poorly understood. Herein we report that the SH2 domain-containing inositol phosphatase (SHIP is phosphorylated upon infection of primary murine macrophages with the genetically related F. novicida, and negatively regulates F. novicida-induced cytokine production. Analyses of the molecular details revealed that in addition to activating the MAP kinases, F. novicida infection also activated the phosphatidylinositol 3-kinase (PI3K/Akt pathway in these cells. Interestingly, SHIP-deficient macrophages displayed enhanced Akt activation upon F. novicida infection, suggesting elevated PI3K-dependent activation pathways in absence of SHIP. Inhibition of PI3K/Akt resulted in suppression of F. novicida-induced cytokine production through the inhibition of NFkappaB. Consistently, macrophages lacking SHIP displayed enhanced NFkappaB-driven gene transcription, whereas overexpression of SHIP led to decreased NFkappaB activation. Thus, we propose that SHIP negatively regulates F. novicida-induced inflammatory cytokine response by antagonizing the PI3K/Akt pathway and suppressing NFkappaB-mediated gene transcription. A detailed analysis of phosphoinositide signaling may provide valuable clues for better understanding the pathogenesis of tularemia.

First report of birds infection by intestinal parasites in Khorramabad, west Iran.

Science.gov (United States)

Badparva, Ebrahim; Ezatpour, Behrouz; Azami, Mehdi; Badparva, Masoud

2015-12-01

Parasitic infections in birds are omnipresent, even when they occur in low amounts, may result in subclinical diseases. There aren't any studies, based on Iranian data, investigating the prevalence of intestinal parasitic infections in some birds' species. We conducted a cross-sectional study between December 2011 and December 2012. The fecal samples were taken from 451 birds including hen, turkey, sparrow, pigeon and decorative birds. The samples screened for intestinal parasitic infections using direct smear, formalin-ether concentration technique, modified Ziehl-Neelsen staining, Culture in RPMI 1640 medium, sporulation with potassium dichromate and Trichrome and Giemsa staining. Out of 451 birds' species, 157 (34.8 %), were infected with one or more type of intestinal parasites. We identified two nematode, two cestoda species and five protozoan parasites species. No trematodes were found in the samples studied. The parasites identified among birds involved Raillietina spp. (4.2 %) and Eimeria spp. (7.1 %) were the most common helminthes and protozoa respectively. From total of birds study, 12 (2.7 %) and 6 (1.3 %) have two and three mixed infections respectively. Intestinal parasitic infections are common in birds in west Iran. The future studies are needed in order to determine to which extent the infections influence mortality and performance of the birds.

Factors Associated with Gastrointestinal Parasitic Infections among Young Population in Northeast Brazil

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Juliana Vasconcelos Lyra da Silva

2016-01-01

Full Text Available Background. Intestinal parasitic infections constitute a major public health problem that is frequently associated with poverty, inadequate sanitation, and the nutritional status of the population. Objective. The aim of the present study is to investigate the possible association of parasitic infections, sanitary conditions, hygiene practices, and the nutritional and socioeconomic status of a poor youth population. Methods. A cross-sectional study was conducted with 367 children and adolescents inhabiting a substandard settlement in the urban area of Maceió (Alagoas State, Brazil. Data collection included socioeconomic status, anthropometric measurements, fecal sample examinations, and laboratory blood analysis. The identification of factors associated with gastrointestinal parasitic infections was undertaken through bi- and multivariate analyses. Results. Stool sample analysis obtained from 300 individuals revealed that 204 (68% were infected with at least one parasite species and of these 130 (63.7% were polyparasitized. No significant associations were identified between low height for age (stunted, parasitic infections, and polyparasitism. There was also no association between family income and parasitosis. However, low socioeconomic status proved to be a potential risk factor for parasitic infections. Conclusion. Actions must be taken to improve sanitation, housing, and environmental conditions in order to eliminate the risk factors for parasitic infections, and thereby guarantee a better quality of life for this population.

Intestinal parasitic infections in HIV infected and non-infected patients in a low HIV prevalence region, West-Cameroon.

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Céline Nguefeu Nkenfou

Full Text Available The magnitude of intestinal parasitic infection in acquired immunodeficiency syndrome patients requires careful consideration in the developing world where poor nutrition is associated with poor hygiene and several tropical diseases. However, there have been very few studies addressing this issue in Cameroon. This study was conducted to determine the prevalence of intestinal parasitosis in HIV/AIDS patients in Dschang -Cameroon. Stool and blood specimens from HIV/AIDS patients and control group were screened respectively for intestinal parasites and for HIV antibodies. Intestinal parasites were identified using direct microscopy, formalin-ether concentration and Ziehl Neelsen methods. Out of 396 participants recruited among patients consulting at hospital, 42 (10.6% were HIV positive, thirty of them treatment naïve. The overall prevalence of intestinal parasites was 14.64%. Out of 42 HIV/AIDS patients, 59.5% (25/42 were infected with intestinal parasites, while only 9.32% (33/354 of the HIV negative patients were infected with intestinal parasites. The parasites detected in our study population included Crystosporidium parvum (2.53%, Entamoeba histolytica (7.52%, Entamoeba coli (4.04%, Giardia lamblia (0.25%, Trichuris trichura (0.25%, Strongyloides stercoralis (0.25% and Taenia spp. (0.25%. In the HIV infected group, Crystosporidium parvum (19.04%, Entamoeba histolytica (19.04%, Entamoeba coli (21.42%, Giardia lamblia (2.38%, Strongyloides stercoralis (0.25% and Taenia spp. (0.25% were found. Crystosporidium parvum was found to be significantly higher in HIV/AIDS patients than in controls (P<0.05. Multivariate analysis showed that the HIV status and the quality of water were the major risk factors for intestinal parasitosis. Routine examinations of stool samples for parasites would significantly benefit the HIV patients by contributing in reducing morbidity and improving the efficiency of antiretroviral treatment. Even after the introduction

Antibodies trap tissue migrating helminth larvae and prevent tissue damage by driving IL-4Rα-independent alternative differentiation of macrophages.

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Julia Esser-von Bieren

Full Text Available Approximately one-third of the world's population suffers from chronic helminth infections with no effective vaccines currently available. Antibodies and alternatively activated macrophages (AAM form crucial components of protective immunity against challenge infections with intestinal helminths. However, the mechanisms by which antibodies target these large multi-cellular parasites remain obscure. Alternative activation of macrophages during helminth infection has been linked to signaling through the IL-4 receptor alpha chain (IL-4Rα, but the potential effects of antibodies on macrophage differentiation have not been explored. We demonstrate that helminth-specific antibodies induce the rapid trapping of tissue migrating helminth larvae and prevent tissue necrosis following challenge infection with the natural murine parasite Heligmosomoides polygyrus bakeri (Hp. Mice lacking antibodies (JH (-/- or activating Fc receptors (FcRγ(-/- harbored highly motile larvae, developed extensive tissue damage and accumulated less Arginase-1 expressing macrophages around the larvae. Moreover, Hp-specific antibodies induced FcRγ- and complement-dependent adherence of macrophages to larvae in vitro, resulting in complete larval immobilization. Antibodies together with helminth larvae reprogrammed macrophages to express wound-healing associated genes, including Arginase-1, and the Arginase-1 product L-ornithine directly impaired larval motility. Antibody-induced expression of Arginase-1 in vitro and in vivo occurred independently of IL-4Rα signaling. In summary, we present a novel IL-4Rα-independent mechanism of alternative macrophage activation that is antibody-dependent and which both mediates anti-helminth immunity and prevents tissue disruption caused by migrating larvae.

Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions.

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Aruna Amarasinghe

Full Text Available Infectious bronchitis virus (IBV causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41 and Connecticut A5968 (Conn A5968 strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.

Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

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Patrícia E. de Almeida

2018-03-01

Full Text Available During Chagas disease, the Trypanosoma cruzi can induce some changes in the host cells in order to escape or manipulate the host immune response. The modulation of the lipid metabolism in the host phagocytes or in the parasite itself is one feature that has been observed. The goal of this mini review is to discuss the mechanisms that regulate intracellular lipid body (LB biogenesis in the course of this parasite infection and their meaning to the pathophysiology of the disease. The interaction host–parasite induces LB (or lipid droplet formation in a Toll-like receptor 2-dependent mechanism in macrophages and is enhanced by apoptotic cell uptake. Simultaneously, there is a lipid accumulation in the parasite due to the incorporation of host fatty acids. The increase in the LB accumulation during infection is correlated with an increase in the synthesis of PGE2 within the host cells and the parasite LBs. Moreover, the treatment with fatty acid synthase inhibitor C75 or non-steroidal anti-inflammatory drugs such as NS-398 and aspirin inhibited the LB biogenesis and also induced the down modulation of the eicosanoid production and the parasite replication. These findings show that LBs are organelles up modulated during the course of infection. Furthermore, the biogenesis of the LB is involved in the lipid mediator generation by both the macrophages and the parasite triggering escape mechanisms.

Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

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Degang Yang

2016-01-01

Full Text Available The persistence of Mycobacterium leprae (M. leprae infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions.Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings.Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

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Yang, Degang; Shui, Tiejun; Miranda, Jake W; Gilson, Danny J; Song, Zhengyu; Chen, Jia; Shi, Chao; Zhu, Jianyu; Yang, Jun; Jing, Zhichun

2016-01-01

The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

Cryptosporidiosis and other intestinal parasitic infections in patients with chronic diarrhea.

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Mahdi, Nadham K; Ali, Naeel H

2004-09-01

To consider the relationship of the parasitic infections including cryptosporidium with chronic diarrhea. Also the effect of chronic disease as pulmonary tuberculosis (TB) and nosocomial infection on the occurrence rate of parasites in cases of chronic diarrhea. Stool samples were collected from 205 patients in teaching, general, child and maternity hospitals in Basrah, Iraq, suffering from chronic diarrhea during 2000. Out of these patients, there were 40 patients with pulmonary TB and 50 inpatients with nosocomial infection. Also 175 apparently healthy individuals who have no episodes of diarrhea for at least 2-months were served as a control group. Direct smear method and then formalin ether sedimentation method were carried out for stool samples to detect intestinal parasites. Fecal smears were prepared from the sediment and stained by the modified Ziehl Neelsen stain for the recovery of red pink oocysts of cryptosporidium. Out of the 205 examined patients, cryptosporidium oocysts were found to be excreted in 20 (9.7%) patients in comparing to 1.1% of the control group. The difference is statistically significant. There were 109 (53.2%) patients found to be positive for intestinal parasitic infections compared to 26 (14.8%) of the control group. The difference is also statistically significant. Out of the 40 TB patients, 2 (5%) were found to excrete cryptosporidium oocysts and also 27 (67.3%) were positive for intestinal parasites. In addition, there were 4 (8%) excreting cryptosporidium oocysts and 23 (46%) infecting by intestinal parasites among the in patients with nosocomial infection. Both acid and non-acid fast parasites should be considered in the differential diagnosis of undiagnosed chronic diarrhea especially among patients with pulmonary TB or nosocomial infection.

Role of Monocyte/Macrophages during HIV/SIV Infection in Adult and Pediatric Acquired Immune Deficiency Syndrome

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Kristen M. Merino

2017-12-01

Full Text Available Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associated with inflammatory disorders and tissue pathogeneses such as occur during HIV infection. Non-human primate research of simian immunodeficiency virus (SIV has been invaluable in better understanding the pathogenesis of HIV infection. The question of HIV/SIV-infected macrophages serving as a viral reservoir has become significant for achieving a cure. In the rhesus macaque model, SIV-infected macrophages have been shown to promote pathogenesis in several tissues resulting in cardiovascular, metabolic, and neurological diseases. Results from human studies illustrated that alveolar macrophages could be an important HIV reservoir and humanized myeloid-only mice supported productive HIV infection and viral persistence in macrophages during ART treatment. Depletion of CD4+ T cells is considered the primary cause for terminal progression, but it was reported that increasing monocyte turnover was a significantly better predictor in SIV-infected adult macaques. Notably, pediatric cases of HIV/SIV exhibit faster and more severe disease progression than adults, yet neonates have fewer target T cells and generally lack the hallmark CD4+ T cell depletion typical of adult infections. Current data show that the baseline blood monocyte turnover rate was significantly higher in neonatal macaques compared to adults and this remained high with disease progression. In this review, we discuss recent data exploring the contribution of monocytes and macrophages to HIV/SIV infection and progression. Furthermore, we highlight the need to further investigate their role in pediatric cases of infection.

Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages.

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Maler, Mareike D; Nielsen, Peter J; Stichling, Nicole; Cohen, Idan; Ruzsics, Zsolt; Wood, Connor; Engelhard, Peggy; Suomalainen, Maarit; Gyory, Ildiko; Huber, Michael; Müller-Quernheim, Joachim; Schamel, Wolfgang W A; Gordon, Siamon; Jakob, Thilo; Martin, Stefan F; Jahnen-Dechent, Willi; Greber, Urs F; Freudenberg, Marina A; Fejer, György

2017-08-01

The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages

Immunodiagnosis of parasitic infections using nuclear techniques

International Nuclear Information System (INIS)

1985-07-01

This report documents the recommendations of the ''Advisory Group on Immunodiagnosis of Parasitic Infections Using Nuclear Techniques'' with a focus on malaria, schistosomiasis and filariasis. Radionuclide tracers are considered an important component of present and future immunological methods for the assessment of the host's humoral and cellular immunity to the parasite and the detection of parasite antigen(s) in human body fluids. The Advisory Group has concluded that there is a continuing need for the development and application of immunodiagnostic methods in parasitic diseases. This report concerns methods which are currently or potentially applicable to immunodiagnostic investigations in parasitic diseases. Reference is made, where appropriate, to recent developments in research which may lead to improvement and standardization of methods now available and the development of new methodology. Separate abstracts on various papers presented were prepared

Prevalence of intestinal parasitic infections among HIV patients in Benin City, Nigeria

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Frederick Olusegun Akinbo

2010-10-01

Full Text Available This study was carried out to determine the presence of intestinal parasites and their correlation with CD4+ T-cell counts and demographics among human immunodeficiency virus (HIV-positive patients in Benin City, Nigeria. Stool specimens from 2,000 HIV-positive patients and 500 controls (HIV-negative individuals were examined for ova, cysts, or parasites, using standard procedures. In addition, patient's blood samples were analyzed for CD4 counts by flow cytometry. An overall prevalence rate of 15.3% was observed among HIV-positive patients while 6.2% was noted among non-HIV subjects. HIV status was a significant (P<0.0001 risk factor for acquiring intestinal parasitic infections. Male gender, CD4 count <200cell/µl, and diarrhea were significantly associated with an increased prevalence of intestinal parasitic infections among HIV-positive patients. The level of education, occupation, and source of water among HIV patients significantly (P<0.0001 affected the prevalence of intestinal parasitic infections. Ascaris lumbricoides was the most predominant parasite in both HIV-positive patients and controls. A CD4 count <200 cells/µl was significantly associated with only Isospora belli and Cryptosporidium infections. The presence of pathogenic intestinal parasites such as A. lumbricoides, hookworm, Giardia intestinalis, Entamoeba histolytica, Trichuris trichiura, and Taenia species among HIV-infected persons should not be neglected. Cryptosporidium species and I. belli were the opportunistic parasites observed in this study. Routine screening for intestinal parasites in HIV-positive patients is advocated.

Climate change and parasite transmission: how temperature affects parasite infectivity via predation on infective stages

NARCIS (Netherlands)

Goedknegt, M.A.; Welsh, J.E.; Drent, J.; Thieltges, D.

2015-01-01

Climate change is expected to affect disease risk in many parasite-host systems, e.g., via an effect of temperature on infectivity (temperature effects). However, recent studies indicate that ambient communities can lower disease risk for hosts, for instance via predation on free-living stages of

Radioimmunoassays and related procedures in the diagnosis of parasitic infections

International Nuclear Information System (INIS)

Dessaint, J.P.; Cesbron, J.Y.; Lutsch, C.; Nogueira-Queiroz, J.A.; Capron, A.

1986-01-01

Immunological tests for the diagnosis of parasitic infections have long been used, yet the marked variability in seroreactivity of infected patients is still a challenge to immunoparasitologists. In the case of helminth parasites, especially schistosomes and filariae, immunoassays have benefited by numerous advances in the characterization and purification of antigens and by the use of monoclonal antibodies. The identification of functional antigens allows the detection of putative protective (or blocking) antibody responses by competitive RIAs using monoclonal antibodies in schistosomiasis. While progress has been made in the investigation of immunity in man, immunoassays for antibodies do not accurately correlate with parasite load, especially at lower antibody responses or after chemotherapy. Immunoassays for circulating parasite antigens have received much attention in recent years. Immunoradiometric assays and related procedures using infection sera or monoclonal antibodies are now being investigated in field conditions. Cross-reactions among circulating antigens from different parasites can decrease the specificity of such assays, whereas circulating immune complexes can interfere with the test. The recent use of RIAs to measure parasite antigens in the urine of patients with schistosomiasis or filariasis appears a promising approach. (author)

Parasitic infections in African pangolin ( Manis temminckii ) from Edo ...

African Journals Online (AJOL)

Amblyomma sp.). Oochoristica sp. (100%) and Amblyomma sp. (75%) were the most prevalent parasites. Both male and female pangolins recorded equal prevalence (100%) of infection, however, mean intensity of parasites was higher in males ...

First report of birds infection by intestinal parasites in Khorramabad, west Iran

OpenAIRE

Badparva, Ebrahim; Ezatpour, Behrouz; Azami, Mehdi; Badparva, Masoud

2014-01-01

Parasitic infections in birds are omnipresent, even when they occur in low amounts, may result in subclinical diseases. There aren’t any studies, based on Iranian data, investigating the prevalence of intestinal parasitic infections in some birds’ species. We conducted a cross-sectional study between December 2011 and December 2012. The fecal samples were taken from 451 birds including hen, turkey, sparrow, pigeon and decorative birds. The samples screened for intestinal parasitic infections ...

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

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McMahon-Pratt, Diane; Saravia, Nancy Gore

2015-01-01

Background Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses. Methodology To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays. Principal Findings Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine

Status of intestinal parasitic infections among residents of Jimma Town, Ethiopia

OpenAIRE

Jejaw, Ayalew; Zeynudin, Ahmed; Zemene, Endalew; Belay, Tariku

2014-01-01

Background Intestinal parasites cause considerable morbidity and mortality in the world, especially in developing countries like Ethiopia. Both urban and rural inhabitants are vulnerable to infection with intestinal parasites in developing countries. The aim of this study was to determine the status of intestinal parasitic infections (IPIs) among residents of Jimma Town, seven years after high prevalence was reported. Results Four hundred and thirty four residents of Jimma Town were included ...

Physiological Correlates of Multiple Parasitic Infections in Side-Blotched Lizards.

Science.gov (United States)

Spence, Austin R; Durso, Andrew M; Smith, Geoffrey D; Skinner, Heather M; French, Susannah S

We investigated the presence of ectoparasites and hemoparasites in side-blotched lizards (Uta stansburiana) across a large part of their range and measured how parasitic infection related to several key physiological indicators of health. Blood samples were collected from 132 lizards from central Arizona, southern Utah, and eastern Oregon. Hemoparasites were found in 22 individuals (3.2% prevalence in Arizona, 19.1% in Utah, and 6.3% in Oregon), and ectoparasites were found on 51 individuals (56.3% prevalence in Arizona, 56.1% in Utah, and 6.7% in Oregon), with 11 individuals infected with both. Hemoparasites and ectoparasites were found in all three states. Immunocompetence was higher in individuals infected with both hemoparasites and ectoparasites. Body condition, glucocorticoid levels, and reproductive investment were not related to infection status. Our study provides evidence that parasitic infection is associated with an active immune system in wild reptiles but may not impose other costs usually associated with parasites.

A cross-sectional study on intestinal parasitic infections in rural communities, northeast Thailand.

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Boonjaraspinyo, Sirintip; Boonmars, Thidarut; Kaewsamut, Butsara; Ekobol, Nuttapon; Laummaunwai, Porntip; Aukkanimart, Ratchadawan; Wonkchalee, Nadchanan; Juasook, Amornrat; Sriraj, Pranee

2013-12-01

Despite the existence of effective anthelmintics, parasitic infections remain a major public health problem in Southeast Asia, including Thailand. In rural communities, continuing infection is often reinforced by dietary habits that have a strong cultural basis and by poor personal hygiene and sanitation. This study presents a survey of the prevalence of intestinal parasitic infections among the people in rural Thailand. The community-based cross-sectional study was conducted in villages in Khon Kaen Province, northeastern Thailand, from March to August 2013. A total of 253 stool samples from 102 males and 140 females, aged 2-80 years, were prepared using formalin-ethyl acetate concentration methods and examined using light microscopy. Ninety-four individuals (37.2%) were infected with 1 or more parasite species. Presence of parasitic infection was significantly correlated with gender (P=0.001); nearly half of males in this survey (49.0%) were infected. Older people had a higher prevalence than younger members of the population. The most common parasite found was Opisthorchis viverrini (26.9%), followed by Strongyloides stercoralis (9.5%), Taenia spp. (1.6%), echinostomes (0.4%), and hookworms (0.4%). The prevalence of intestinal protozoa was Blastocystis hominis 1.6%, Entamoeba histolytica 0.8%, Entamoeba coli 0.8%, Balantidium coli 0.4%, Iodamoeba bütschlii 0.4%, and Sarcocystis hominis 0.4%. Co-infections of various helminths and protozoa were present in 15.9% of the people. The present results show that the prevalence of parasitic infections in this region is still high. Proactive education about dietary habits, personal hygiene, and sanitation should be provided to the people in this community to reduce the prevalence of intestinal parasite infections. Moreover, development of policies and programs to control parasites is needed.

Gastrointestinal parasitic infection, anthropometrics, nutritional status, and physical work capacity in Colombian boys.

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Wilson, W.M.; Dufour, D.L.; Staten, L.K.; Barac-Nieto, M.; Reina, J.C.; Spurr, G.B.

1999-11-01

This article tests the hypothesis that the presence of gastrointestinal parasites in Colombian boys is negatively associated with anthropometric characteristics, physical work capacity, blood hemoglobin (Hb) levels, and nutritional status. Anthropometric, Hb, &Vdot;O(2) max, and parasite load data were collected on 1,016 boys in Cali, Colombia. The boys were classified as lower socioeconomic class (SEC) from either urban or rural environments, and upper SEC from an urban environment. Sixty-three percent of the boys were infected with gastrointestinal parasites and, of the infected boys, 80-95% had light parasite loads. Parasites found included Necator americanus, Ascaris lumbricoides, Entamoeba histolytica, Trichuris trichiura, Giardia spp., and Enterobius vermicularis. Infected boys had significantly lower weight, stature, weight-for-height (among 6-9-year-old boys), Hb levels, and &Vdot;O(2) max (ANCOVA, controlling for age and SEC). In terms of nutritional status, infected boys were 1.47 times more likely to be classified as iron deficient than noninfected boys (chi-square, P nutritional status of populations in regions endemic for parasitic infection should include testing for the presence of infection. Am. J. Hum. Biol. 11:763-771, 1999. Copyright 1999 Wiley-Liss, Inc.

Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

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Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

2017-09-01

American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

Human innate lymphoid cells (ILCs) in filarial infections.

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Bonne-Année, S; Nutman, T B

2018-02-01

Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Prevalence of parasitic infections in HIV-positive patients in southern Ethiopia: a cross-sectional study.

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Fekadu, Sintayehu; Taye, Kefyalew; Teshome, Wondu; Asnake, Solomon

2013-11-15

Intestinal parasitic infections are a major public health burden in tropical countries. Although all HIV/AIDS patients are susceptible to parasitic infections, those having lower immune status are at greater risk. The aim of this study was to determine the prevalence of intestinal parasitic infections in patients living with HIV/AIDS. This was a facility-based cross-sectional study. A total of 343 consecutively sampled HIV/AIDS patients from the HIV care clinic of Hawassa University Referral Hospital were included. Subjects were interviewed for demographic variables and diarrheal symptoms using structured questionnaires. Stool examinations and CD4 cells counts were also performed. The prevalence of intestinal parasitic infection was 47.8% among HIV/AIDS patients; single helminthic infection prevalence (22.7%) was higher than that the prevalence of protozoal infections (14.6%). About 54% of study participants had chronic diarrhea while 3.4% had acute diarrhea. The prevalence of intestinal parasites in patients with chronic diarrhea was significantly higher than in acute diarrhea (p intestinal parasite infections such as Ascaris lumbricoides, Taenia spp., and hookworm were commonly found, regardless of immune status or diarrheal symptoms. Opportunistic and non-opportunistic intestinal parasitic infection were more frequent in patients with a CD4 count of Intestinal parasitic infections should be suspected in HIV/AIDS-infected patients with advanced disease presenting with chronic diarrhea. Patients with low CD4 counts should be examined critically for intestinal parasites, regardless of diarrheal status.

Pseudomonas aeruginosa infection alters the macrophage phenotype switching process during wound healing in diabetic mice.

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Chen, Sinuo; Li, Renren; Cheng, Chun; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Wang, Juan; Zhang, Jieping; Zhang, Jingfa; Wang, Hong; Lu, Lixia; Xu, Guo-Tong; Tian, Haibin

2018-03-07

Macrophages play critical roles in wound healing process. They switch from "classically activated" (M1) phenotype in the early inflammatory phase to "alternatively activated" (M2) phenotype in the later healing phase. However, the dynamic process of macrophage phenotype switching in diabetic wounds burdened with bacteria is unclear. In this report, Pseudomonas aeruginosa, frequently detected in diabetic foot ulcers, was inoculated into cutaneous wounds of db/db diabetic mice to mimic bacterium-infected diabetic wound healing. We observed that P. aeruginosa infection impaired diabetic wound healing and quickly promoted the expression of pro-inflammatory genes (M1 macrophage markers) tumor necrosis factor-α (tnf-α), interleukin-1β (il-1β) and il-6 in wounds. The expression of markers of M2 macrophages, including il-10, arginase-1, and ym1 were also upregulated. In addition, similar gene expression patterns were observed in macrophages isolated directly from wounds. Immunostaining showed that P. aeruginosa infection increased both the ratios of M1 and M2 macrophages in wounds compared with that in control groups, which was further confirmed by in vitro culturing macrophages with P. aeruginosa and skin fibroblast conditioned medium. However, the ratios of the expression levels of pro-inflammatory genes to anti-inflammatory gene il-10 was increased markedly in P. aeruginosa infected wounds and macrophages compared with that in control groups, and P. aeruginosa prolonged the presence of M1 macrophages in the wounds. These data demonstrated that P. aeruginosa in diabetic wounds activates a mixed M1/M2 macrophage phenotype with an excessive activation of M1 phenotype or relatively inadequate activation of M2 phenotype. © 2018 International Federation for Cell Biology.

Nutritional status, intestinal parasite infection and allergy among school children in northwest Ethiopia.

Science.gov (United States)

Amare, Bemnet; Ali, Jemal; Moges, Beyene; Yismaw, Gizachew; Belyhun, Yeshambel; Gebretsadik, Simon; Woldeyohannes, Desalegn; Tafess, Ketema; Abate, Ebba; Endris, Mengistu; Tegabu, Desalegn; Mulu, Andargachew; Ota, Fusao; Fantahun, Bereket; Kassu, Afework

2013-01-12

Parasitic infections have been shown to have deleterious effects on host nutritional status. In addition, although helmintic infection can modulate the host inflammatory response directed against the parasite, a causal association between helminths and allergy remains uncertain. The present study was therefore designed to evaluate the relationship between nutritional status, parasite infection and prevalence of allergy among school children. A cross sectional study was performed involving school children in two elementary schools in Gondar, Ethiopia. Nutritional status of these children was determined using anthropometric parameters (weight-for-age, height-for-age and BMI-for-age). Epi-Info software was used to calculate z-scores. Stool samples were examined using standard parasitological procedures. The serum IgE levels were quantified by total IgE ELISA kit following the manufacturer's instruction. A total of 405 children (with mean age of 12.09.1 ± 2.54 years) completed a self-administered allergy questionnaire and provided stool samples for analysis. Overall prevalence of underweight, stunting and thinness/wasting was 15.1%, 25.2%, 8.9%, respectively. Of the total, 22.7% were found to be positive for intestinal parasites. The most prevalent intestinal parasite detected was Ascaris lumbricoides (31/405, 7.6%). There was no statistically significant association between prevalence of malnutrition and the prevalence of parasitic infections. Median total serum IgE level was 344 IU/ml (IQR 117-2076, n=80) and 610 IU/ml (143-1833, n=20), respectively, in children without and with intestinal parasite infection (Z=-0.198, P>0.8). The prevalence of self reported allergy among the subset was 8%. IgE concentration was not associated either with the presence of parasitic infection or history of allergy. The prevalence of malnutrition, intestinal parasitism and allergy was not negligible in this population. In addition, there was no significant association between the

Evidence that leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism

International Nuclear Information System (INIS)

Wilson, M.E.; Pearson, R.D.

1986-01-01

The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extracellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. Remarkable similarities have been found between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands; that is mannan, mannose-BSA and fucose-BSA. In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of 125 I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4%. Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion. Additionally, NH 4 Cl decreased macrophage ingestion of promastigotes by 38.2%. Subinhibitory concentration of NH 4 Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parsite ingestion by 76.4%

Unique physiology of host-parasite interactions in microsporidia infections.

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Williams, Bryony A P

2009-11-01

Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.

Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection.

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Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Savelkoul, Paul H M; Stassen, Frank R M

2017-11-13

During infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Using a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria. Bacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

Science.gov (United States)

Jagoe, R. Thomas; Jarman, Elizabeth R.; North, James C.; Pridmore, Alison; Musaya, Janelisa; French, Neil; Zijlstra, Eduard E.; Molyneux, Malcolm E.; Read, Robert C.

2013-01-01

We tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-γ) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8+ lymphocytes with activated phenotype. Toll-like receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-γ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci. PMID:23576675

Parasitic infections associated with febrile conditions in Imo State ...

African Journals Online (AJOL)

Urinary tract parasites, which included Trichomonas. vaginalis and Schistosoma haematobium, were found in 330(6.87%) of the study population and hemoparasites (P. falciparum and Onchocerca spp.) in 1260(26.25%). Mixed infections of gastrointestinal and hemoparasites, gastrointestinal and urinary tract parasites, ...

Impacts of parasite infection on columnaris disease of tilapia

Science.gov (United States)

There is no information available on whether parasite infection will increase the susceptibility of tilapia to Flavobacterium columnare and whether parasite treatment could improve fish survival after F. columnare exposure. Two trials were conducted to evaluate 1) the susceptibility of hybrid tilapi...

ISG15 governs mitochondrial function in macrophages following vaccinia virus infection.

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Sara Baldanta

2017-10-01

Full Text Available The interferon (IFN-stimulated gene 15 (ISG15 encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM after vaccinia virus (VACV infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS were pathways altered in ISG15-/- BMDM treated with IFN. Mitochondrial respiration, Adenosine triphosphate (ATP and reactive oxygen species (ROS production was higher in ISG15+/+ BMDM than in ISG15-/- BMDM following IFN treatment, indicating the involvement of ISG15-dependent mechanisms. An additional consequence of ISG15 depletion was a significant change in macrophage polarization. Although infected ISG15-/- macrophages showed a robust proinflammatory cytokine expression pattern typical of an M1 phenotype, a clear blockade of nitric oxide (NO production and arginase-1 activation was detected. Accordingly, following IFN treatment, NO release was higher in ISG15+/+ macrophages than in ISG15-/- macrophages concomitant with a decrease in viral titer. Thus, ISG15-/- macrophages were permissive for VACV replication following IFN treatment. In conclusion, our results demonstrate that ISG15 governs the dynamic functionality of mitochondria, specifically, OXPHOS and mitophagy, broadening its physiological role as an antiviral agent.

Tacaribe virus but not junin virus infection induces cytokine release from primary human monocytes and macrophages.

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Allison Groseth

Full Text Available The mechanisms underlying the development of disease during arenavirus infection are poorly understood. However, common to all hemorrhagic fever diseases is the involvement of macrophages as primary target cells, suggesting that the immune response in these cells may be of paramount importance during infection. Thus, in order to identify features of the immune response that contribute to arenavirus pathogenesis, we have examined the growth kinetics and cytokine profiles of two closely related New World arenaviruses, the apathogenic Tacaribe virus (TCRV and the hemorrhagic fever-causing Junin virus (JUNV, in primary human monocytes and macrophages. Both viruses grew robustly in VeroE6 cells; however, TCRV titres were decreased by approximately 10 fold compared to JUNV in both monocytes and macrophages. Infection of both monocytes and macrophages with TCRV also resulted in the release of high levels of IL-6, IL-10 and TNF-α, while levels of IFN-α, IFN-β and IL-12 were not affected. However, we could show that the presence of these cytokines had no direct effect on growth of either TCRV of JUNV in macrophages. Further analysis also showed that while the production of IL-6 and IL-10 are dependent on viral replication, production of TNF-α also occurs after exposure to UV-inactivated TCRV particles and is thus independent of productive virus infection. Surprisingly, JUNV infection did not have an effect on any of the cytokines examined indicating that, in contrast to other viral hemorrhagic fever viruses, macrophage-derived cytokine production is unlikely to play an active role in contributing to the cytokine dysregulation observed in JUNV infected patients. Rather, these results suggest that an early, controlled immune response by infected macrophages may be critical for the successful control of infection of apathogenic viruses and prevention of subsequent disease, including systemic cytokine dysregulation.

HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon

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Gilda Tachedjian

2013-09-01

Full Text Available The proline repeat motif (PxxP of Nef is required for interaction with the SH3 domains of macrophage-specific Src kinase Hck. However, the implication of this interaction for viral replication and infectivity in macrophages and T lymphocytes remains unclear. Experiments in HIV-1 infected macrophages confirmed the presence of a Nef:Hck complex which was dependent on the Nef proline repeat motif. The proline repeat motif of Nef also enhanced both HIV-1 infection and replication in macrophages, and was required for incorporation of Hck into viral particles. Unexpectedly, wild-type Hck inhibited infection of macrophages, but Hck was shown to enhance infection of primary T lymphocytes. These results indicate that the interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. Hck-dependent enhancement of HIV-1 infection of T cells suggests that Nef-Hck interaction may contribute to the spread of HIV-1 infection from macrophages to T cells by modulating events in the producer cell, virion and target cell.

Prevalence of opportunistic intestinal parasitic infection among HIV infected patients who are taking antiretroviral treatment at Jimma Health Center, Jimma, Ethiopia.

Science.gov (United States)

Zeynudin, A; Hemalatha, K; Kannan, S

2013-02-01

One of the major health problems among HIV sero-positive patients are superimposed infections due to the deficient immunity. Furthermore, intestinal parasitic (IP) infections, which are also one of the basic health problems in tropical regions, are common in these patients. Infection by opportunistic pathogens, including various forms of intestinal parasites has been the hall mark of HIV since the beginning of the epidemic. To study the prevalence of opportunistic intestinal parasitic infection among HIV patients who are taking antiretroviral treatment (ART) in Jimma, Ethiopia. Patient samples were diagnosed by examination of single stool specimen which was examined as fresh wet mounts, formal-ether concentration technique and modified Ziehl-Neelsen staining technique. Data was obtained from 91 study subjects selected by convenience sampling method. The overall prevalence of intestinal parasitic infections was found to be 39.56%. Eight types of intestinal parasites was identified, the most dominant being, Ascaris lumbricoides, 21.67%, Entamoeba histolytica, 15% and Cryptosporidium parvum 13.33%. The prevalence of opportunistic parasite was 15.38%, the prevalence of non-opportunistic parasite was 20.87% and the prevalence of both opportunistic and non opportunistic was 3.29%. The study indicated that intestinal parasites were still a problem in the study area. Data also showed that among the predisposing factors, habit of hand washing before meal, usage of latrine and duration after treatment was statistically associated with intestinal parasitic infections.

Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.

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William J B Vincent

Full Text Available Immune cells sense and react to a multitude of factors including both host and microbe-derived signals. Understanding how cells translate these cues into particular cellular behaviors is a complex yet critical area of study. We have previously shown that both neutrophils and macrophages are important for controlling the fish pathogen Streptococcus iniae. Here, we report both host and bacterial determinants leading to the formation of organized macrophage aggregates as part of the host inflammatory response in a subset of infected larvae. Streptococcal capsule was a required signal for aggregate formation. Macrophage aggregation coincided with NFκB activity, and the formation of these aggregates is mediated by leukotriene B4 (LTB4 produced by neutrophils. Depletion, inhibition, or genetic deletion of leukotriene A4 hydrolase (Lta4h, which catalyzes the last step in LTB4 synthesis, resulted in the absence of macrophage aggregation. Larvae with impaired neutrophil function also had impaired macrophage aggregation; however, aggregate formation was partially rescued with the addition of exogenous LTB4. Neutrophil-specific expression of lta4h was sufficient to rescue macrophage aggregation in Lta4h-deficient larvae and increased host survival following infection. In summary, our findings highlight a novel innate immune response to infection in which specific bacterial products drive neutrophils that modulate macrophage behavior through eicosanoid signaling.

Global issues in allergy and immunology: Parasitic infections and allergy.

Science.gov (United States)

Cruz, Alvaro A; Cooper, Philip J; Figueiredo, Camila A; Alcantara-Neves, Neuza M; Rodrigues, Laura C; Barreto, Mauricio L

2017-11-01

Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of "classical" allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Status of intestinal parasitic infections among residents of Jimma Town, Ethiopia.

Science.gov (United States)

Jejaw, Ayalew; Zeynudin, Ahmed; Zemene, Endalew; Belay, Tariku

2014-08-07

Intestinal parasites cause considerable morbidity and mortality in the world, especially in developing countries like Ethiopia. Both urban and rural inhabitants are vulnerable to infection with intestinal parasites in developing countries. The aim of this study was to determine the status of intestinal parasitic infections (IPIs) among residents of Jimma Town, seven years after high prevalence was reported. Four hundred and thirty four residents of Jimma Town were included in this study. By the cross-sectional survey, the overall prevalence of intestinal parasites was 209 (48.2%). Nine species of intestinal parasites were isolated, Ascaris lumbricoides and Trichuris trichiura being the most predominant. Residence in Hermata Mentina kebele, Adjusted Odds Ratio (AOR), 3.0, 95% CI, 1.71-5.39), age less than 10 years (AOR, 3.7, 95% CI, 1.33-10.36), illiteracy (AOR, 3.2, 95% CI, 1.64-6.19), estimated monthly family income of less than 500 Ethiopian Birr (AOR, 2.9, 95% CI, 1.32-4.90) and irregular washing hands before meal (AOR, 5.3, 95% CI, 1.36-21.07) were predictors of IPI in this study. The retrospective study revealed a significant decrease (P = 0.037) in the proportion of patients infected with intestinal parasites out of those who requested stool examination over the six-year period. This study confirms that IPIs are still common among residents of Jimma Town. Nearly half of the study participants were infected with at least one intestinal parasite. Public health interventions targeting prevention of IPIs should be strengthened in Jimma Town.

Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF).

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Yamamoto, Nobuto; Ushijima, Naofumi; Koga, Yoshihiko

2009-01-01

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of HIV-infected patients was lost or reduced because Gc protein is deglycosylated by alpha-N-acetylgalactosaminidase (Nagalase) secreted from HIV-infected cells. Therefore, macrophages of HIV-infected patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Since Nagalase is the intrinsic component of the envelope protein gp120, serum Nagalase activity is the sum of enzyme activities carried by both HIV virions and envelope proteins. These Nagalase carriers were already complexed with anti-HIV immunoglobulin G (IgG) but retained Nagalase activity that is required for infectivity. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage activating factor (termed GcMAF), which produces no side effects in humans. Macrophages activated by administration of 100 ng GcMAF develop a large amount of Fc-receptors as well as an enormous variation of receptors that recognize IgG-bound and unbound HIV virions. Since latently HIV-infected cells are unstable and constantly release HIV virions, the activated macrophages rapidly intercept the released HIV virions to prevent reinfection resulting in exhaustion of infected cells. After less than 18 weekly administrations of 100 ng GcMAF for nonanemic patients, they exhibited low serum Nagalase activities equivalent to healthy controls, indicating eradication of HIV-infection, which was also confirmed by no infectious center formation by provirus inducing agent-treated patient PBMCs. No recurrence occurred and their healthy CD + cell counts were maintained for 7 years.

Effects of trans-stilbene and terphenyl compounds on different strains of Leishmania and on cytokines production from infected macrophages.

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Bruno, Federica; Castelli, Germano; Vitale, Fabrizio; Giacomini, Elisa; Roberti, Marinella; Colomba, Claudia; Cascio, Antonio; Tolomeo, Manlio

2018-01-01

Most of the antileishmanial modern therapies are not satisfactory due to high toxicity or emergence of resistance and high cost of treatment. Previously, we observed that two compounds of a small library of trans-stilbene and terphenyl derivatives, ST18 and TR4, presented the best activity and safety profiles against Leishmania infantum promastigotes and amastigotes. In the present study we evaluated the effects of ST18 and the TR4 in 6 different species of Leishmania and the modifications induced by these two compounds in the production of 8 different cytokines from infected macrophages. We observed that TR4 was potently active in all Leishmania species tested in the study showing a leishmanicidal activity higher than that of ST18 and meglumine antimoniate in the most of the species. Moreover, TR4 was able to decrease the levels of IL-10, a cytokine able to render the host macrophage inactive allowing the persistence of parasites inside its phagolysosome, and increase the levels of IL-1β, a cytokine important for host resistance to Leishmania infection by inducible iNOS-mediated production of NO, and IL-18, a cytokine implicated in the development of Th1-type immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Nutritional status, intestinal parasite infection and allergy among school children in Northwest Ethiopia

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Amare Bemnet

2013-01-01

Full Text Available Abstract Background Parasitic infections have been shown to have deleterious effects on host nutritional status. In addition, although helmintic infection can modulate the host inflammatory response directed against the parasite, a causal association between helminths and allergy remains uncertain. The present study was therefore designed to evaluate the relationship between nutritional status, parasite infection and prevalence of allergy among school children. Methods A cross sectional study was performed involving school children in two elementary schools in Gondar, Ethiopia. Nutritional status of these children was determined using anthropometric parameters (weight-for-age, height-for-age and BMI-for-age. Epi-Info software was used to calculate z-scores. Stool samples were examined using standard parasitological procedures. The serum IgE levels were quantified by total IgE ELISA kit following the manufacturer’s instruction. Result A total of 405 children (with mean age of 12.09.1 ± 2.54 years completed a self-administered allergy questionnaire and provided stool samples for analysis. Overall prevalence of underweight, stunting and thinness/wasting was 15.1%, 25.2%, 8.9%, respectively. Of the total, 22.7% were found to be positive for intestinal parasites. The most prevalent intestinal parasite detected was Ascaris lumbricoides (31/405, 7.6%. There was no statistically significant association between prevalence of malnutrition and the prevalence of parasitic infections. Median total serum IgE level was 344 IU/ml (IQR 117–2076, n = 80 and 610 IU/ml (143–1833, n = 20, respectively, in children without and with intestinal parasite infection (Z = −0.198, P > 0.8. The prevalence of self reported allergy among the subset was 8%. IgE concentration was not associated either with the presence of parasitic infection or history of allergy. Conclusion The prevalence of malnutrition, intestinal parasitism and allergy was not

PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

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Isidro Jarque

2016-07-01

Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

Prevalence of Intestinal Parasitic Infections Among Primary School Children in Bushehr, Iran

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Barazesh

2016-08-01

Full Text Available Background Due to their weak immune systems, contact with soil, and failure to comply with hygiene principles, the prevalence of intestinal parasitic infection is high among children. Objectives This study was conducted to determine the prevalence of intestinal parasitic infection and the effects of various factors among elementary school children in Bushehr, Iran. Methods Following coordination with the education office, schools were randomly selected from different areas, and fecal samples were collected from 203 males and females students at different education levels. The samples were examined using the formalin-ether sedimentation technique. The data were collected via questionnaires and analyzed using SPSS 18.0 and the Chi-squared test. Results Approximately 25.1% of the children were infected with at least one type of intestinal parasite, and 5.9% of them were infected with more than one species. The highest prevalence was apparent in children at education levels 4 and 5. There was no significant relationship between infection and parents’ education and some clinical symptoms, such as abdominal pain, loss of appetite, and nausea, but there was a significant relationship with the number of family members. Conclusions The prevalence of intestinal parasitic infections was relatively high among the schoolchildren in this study. Since these parasites can cause anemia and dysfunctional nutrient absorption, growth, and learning among children, it is suggested that training courses be held for parents and that basic steps be taken to improve the level of hygiene in the region to prevent the transmission of these parasites.

MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

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Helena Westerdahl

Full Text Available Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load and infection status (infected or not. It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

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Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

2013-01-01

Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

Prevalence of Intestinal Parasitic Infections Among People in Baghmalek During 2013 ‒ 2014

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Khoshnood

2015-04-01

Full Text Available Background Intestinal parasitic infections are one of major health problems, especially in developing countries. Several factors, such as geographical location and socioeconomic conditions, are responsible for variations in the prevalence of intestinal parasites. Baghmalek is an area in Khuzestan, a western province of Iran. This area has a mild climate and is a touristic region of the province. Objectives The aim of our study was to describe the occurrence of intestinal parasitic infections in Baghmalek city, southwest of Iran. Patients and Methods The study was carried out from October 2013 to October 2014. A total of 8469 human stool samples were examined by microscopy methods. Separation of samples, based on age, sex and season was done and data were analyzed with the SPSS software. Results Totally, 1131 (13.35% samples were positive for intestinal parasites. It was found that prevalence of intestinal parasitic infections was higher in males than in females. The greatest prevalence (45% was in the group of the under 15 years old and the prevalence rate of intestinal parasites infection was higher in summer (18.53% compared to seasons (P < 0.05. Conclusions Because the intestinal parasitic infections are a health concern in areas with poor nutritional and socioeconomic status, intervention programs, including health education and environmental sanitation, are required.

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

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Twu, Olivia; Dessí, Daniele; Vu, Anh; Mercer, Frances; Stevens, Grant C; de Miguel, Natalia; Rappelli, Paola; Cocco, Anna Rita; Clubb, Robert T; Fiori, Pier Luigi; Johnson, Patricia J

2014-06-03

The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

Digital holographic microscopy as a technique to monitor macrophages infected by leishmania

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Mendoza-Rodríguez, E.; Organista-Castelblanco, C.; Camacho, M.; Monroy-Ramírez, F.

2017-06-01

The Digital Holographic Microscopy in Transmission technique (DHM) is considered a useful tool in the noninvasive quantifying of transparent biological objects like living cells. In this work, we propose this technique to study and to monitor control macrophages infected by Leishmania (mouse lineJ774.A1). When the promastigotes enter in contact with healthy macrophages, they got phagocytosed and latterly confined in the formed parasitophorous vacuole. These processes change the morphology and density of the host macrophage. Both parameters can be measured in a label-free analysis of cells with the aid of the DHM technique. Our technique begins with the optical record of the holograms using a modified Mach-Zehnder interferometer and the reconstruction of the complex optical field transmitted by macrophages. In the latter point, we employ the angular spectrum algorithm. With the complex optical field reconstruction, we compute the field amplitude and the phase difference maps, which leads to describe one morphological characterization for the samples. Using phase difference maps is possible to measure internal variations for the integral refractive index, estimating the infection level of macrophages. Through the changes in the integral refractive index, it is also possible to describe and quantify in two different states the evolution of the infection. With these results some parameters of cells have been quantified, making the DHM technique a viable tool for diagnosis of biological samples under the presence of some pathogen.

The controversy of parasitic infection in pediatric appendicitis: a ...

African Journals Online (AJOL)

... of the operative findings during surgery. Postoperative complications, if any, and the histopathology reports of the removed appendices were also studied. Patients were divided into two groups according to the presence or the absence of parasites in the appendix lumen. In group I (n= 98), parasitic infection was observed, ...

Parasitic loads in tissues of mice infected with Trypanosoma cruzi and treated with AmBisome.

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Sabrina Cencig

2011-06-01

Full Text Available BACKGROUND: Chagas disease is one of the most important public health problems and a leading cause of cardiac failure in Latin America. The currently available drugs to treat T. cruzi infection (benznidazole and nifurtimox are effective in humans when administered during months. AmBisome (liposomal amphotericin B, already shown efficient after administration for some days in human and experimental infection with Leishmania, has been scarcely studied in T. cruzi infection. AIMS: This work investigates the effect of AmBisome treatment, administered in 6 intraperitoneal injections at various times during acute and/or chronic phases of mouse T. cruzi infection, comparing survival rates and parasitic loads in several tissues. METHODOLOGY: Quantitative PCR was used to determine parasitic DNA amounts in tissues. Immunosuppressive treatment with cyclophosphamide was used to investigate residual infection in tissues. FINDINGS: Administration of AmBisome during the acute phase of infection prevented mice from fatal issue. Parasitaemias (microscopic examination were reduced in acute phase and undetectable in chronic infection. Quantitative PCR analyses showed significant parasite load reductions in heart, liver, spleen, skeletal muscle and adipose tissues in acute as well as in chronic infection. An earlier administration of AmBisome (one day after parasite inoculation had a better effect in reducing parasite loads in spleen and liver, whereas repetition of treatment in chronic phase enhanced the parasite load reduction in heart and liver. However, whatever the treatment schedule, cyclophosphamide injections boosted infection to parasite amounts comparable to those observed in acutely infected and untreated mice. CONCLUSIONS: Though AmBisome treatment fails to completely cure mice from T. cruzi infection, it impedes mortality and reduces significantly the parasitic loads in most tissues. Such a beneficial effect, obtained by administrating it over a short

Effects of Parasitic Infections on Erythrocyte Indices of Camels in Nigeria

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Jalailudeen Lawal Rabana

2011-03-01

Full Text Available This study was conducted to determine the prevalence and effect of parasitic infection on erythrocyte indices in trade camels slaughtered in Maiduguri, Nigeria. Two hundred adult one humped camels comprised of 87 (43.5 % males and 113 (56.5 % females were examined for helminths and hemoparasites at their slaughter time according to the standard procedures. An overall prevalence of 79 % for single and mixed infections was observed. Examination of faecal samples from camels shows 82 (41 % were harbouring different nematodes, mostly Strongyle, Strongyloides and Hemonchus species. Buffy coat and thin smear examination of blood samples showed Babesia and Anaplasma species. More females (44.5 % than males (34.5 % were positive for various parasitic infections. But the percentage was not statistically significant (P > 0.05. Packed cell volume (PCV, mean haemoglobin concentration (MCH, mean corpuscular haemoglobin concentration (MCHC and red blood cell counts were significantly (P < 0.01 affected in the infected camels compared to the non-infected ones. Parasite infection in camels leads to macrocytic anaemia.

Parasitic infections and maternal anaemia among expectant mothers in the Dangme East District of Ghana.

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Tay, Samuel Crowther Kofi; Nani, Emmanuel Agbeko; Walana, Williams

2017-01-03

Parasitic infections are of public health concern globally, particular among at risk groups such as pregnant women in developing countries. The presence of these parasites during pregnancy potentiate adverse effects to both the mother and the unborn baby. This study sought to establish the prevalence of some parasitic agents among antenatal attendees in the Dangme East District of Ghana. A cross-sectional prospective study was conduct between April and July, 2012. Venous blood specimens were collected from each participant for haemoglobin estimation and malaria microscopy. In addition participants' early morning mid-stream urine and stool specimens were analyzed microscopically for parasitic agents. A total of 375 pregnant women were involved in the study, of which anaemia was present in 66.4% (249/375). However, parasitic infections associated anaemia prevalence was 49.6% (186/375). In all, 186 cases of parasitic infections were observed; 171 (44.0%) were single isolated infections while 15 (4.0%) were co-infections. Plasmodium species were significantly associated with anaemia (13.3%, χ 2  = 23.290, p anaemia in pregnancy. Except where co-infections exist (3.7%, χ 2  = 11.267, p = 0.001), the rest of the single infections were insignificantly associated with anaemia. Collectively, intestinal helminthes were predominantly significant with anaemia in pregnancy (p = 0.001, χ 2  = 107.800). The study revealed relatively high prevalence of parasitic infections among the study population, suggesting that about three-quarters of the anaemic mothers are either single or co-infected with parasitic agents.

Of poisons and parasites-the defensive role of tetrodotoxin against infections in newts.

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Johnson, Pieter T J; Calhoun, Dana M; Stokes, Amber N; Susbilla, Calvin B; McDevitt-Galles, Travis; Briggs, Cheryl J; Hoverman, Jason T; Tkach, Vasyl V; de Roode, Jacobus C

2018-02-24

Classical research on animal toxicity has focused on the role of toxins in protection against predators, but recent studies suggest these same compounds can offer a powerful defense against parasites and infectious diseases. Newts in the genus Taricha are brightly coloured and contain the potent neurotoxin, tetrodotoxin (TTX), which is hypothesized to have evolved as a defense against vertebrate predators such as garter snakes. However, newt populations often vary dramatically in toxicity, which is only partially explained by predation pressure. The primary aim of this study was to evaluate the relationships between TTX concentration and infection by parasites. By systematically assessing micro- and macroparasite infections among 345 adult newts (sympatric populations of Taricha granulosa and T. torosa), we detected 18 unique taxa of helminths, fungi, viruses and protozoans. For both newt species, per-host concentrations of TTX, which varied from undetectable to >60 μg/cm 2 skin, negatively predicted overall parasite richness as well as the likelihood of infection by the chytrid fungus, Batrachochytrium dendrobatidis, and ranavirus. No such effect was found on infection load among infected hosts. Despite commonly occurring at the same wetlands, T. torosa supported higher parasite richness and average infection load than T. granulosa. Host body size and sex (females > males) tended to positively predict infection levels in both species. For hosts in which we quantified leucocyte profiles, total white blood cell count correlated positively with both parasite richness and total infection load. By coupling data on host toxicity and infection by a broad range of micro- and macroparasites, these results suggest that-alongside its effects on predators-tetrodotoxin may help protect newts against parasitic infections, highlighting the importance of integrative research on animal chemistry, immunological defenses and natural enemy ecology. © 2018 The Authors. Journal

Use of irradiation to control infectivity of food-borne parasites

International Nuclear Information System (INIS)

1993-01-01

Food-borne parasitic diseases are common throughout the world, pose significant health problems and cause economic losses in terms of agricultural commodities and human productivity. The diseases usually occur through consumption of raw or partially cooked foods with are infected by various parasites (e.g. tapeworms, roundworms, flukes, parasitic protozoa, etc.). The problem is significant in developing countries where the population has the habit of consuming raw food of animal origin. Available data, with the exception of data on Trichinella spiralis, a parasitic nematode, were insufficient for the use of irradiation technology to control food-borne parasites. Therefore, a Co-ordinated Research Programme (CRP) on the Use of Irradiation to Control Infectivity of Food-Borne Parasites was implemented by the FAO/IAEA in 1986. The results of the work carried out over five years (1986-1991) by twelve researchers participating in the programme, have established conclusively the potential for application of food irradiation in the control of liver flukes, tapeworms, roundworms, trichinosis, toxoplasmosis, etc. This report includes the conclusions and recommendations of the participants concerning the results obtained and need for further research. Refs, figs and tabs

Trypanosoma cruzi: blood parasitism kinetics and their correlation with heart parasitism intensity during long-term infection of Beagle dogs

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Vanja M Veloso

2008-09-01

Full Text Available The goals of the present study were to evaluate the kinetics of blood parasitism by examination of fresh blood, blood culture (BC and PCR assays and their correlation with heart parasitism during two years of infection in Beagle dogs inoculated with the Be-78, Y and ABC Trypanosoma cruzi strains. Our results showed that the parasite or its kDNA is easily detected during the acute phase in all infected animals. On the other hand, a reduced number of positive tests were verified during the chronic phase of the infection. The frequency of positive tests was correlated with T. cruzi strain. The percentage of positive BC and blood PCR performed in samples from animals inoculated with Be-78 and ABC strains were similar and significantly larger in relation to animals infected with the Y strain.Comparison of the positivity of PCR tests performed using blood and heart tissue samples obtained two years after infection showed two different patterns associated with the inoculated T. cruzi strain: (1 high PCR positivity for both blood and tissue was observed in animals infected with Be-78 or ABC strains; (2 lower and higher PCR positivity for the blood and tissue, respectively, was detected in animals infected with Y strains. These data suggest that the sensitivity of BC and blood PCR was T. cruzi strain dependent and, in contrast, the heart tissue PCR revealed higher sensitivity regardless of the parasite stock.

Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae

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Camberlein, Emilie; Cohen, Jonathan M.; José, Ricardo; Hyams, Catherine J.; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A.; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad

2015-01-01

Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. PMID:25583525

Are soil and waterborne parasitic infections health risk for worker populations in southeast Turkey?

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Sibel Ak

2017-06-01

Full Text Available Objective: The soil and waterborne parasitic infections rate is high degree in developed and developing countries. Migratory workers have greater exposure to these parasitic infections and a lot of morbidity due to these infections in workers. For this reason, we aimed to investigate the presence of soil and waterborne parasites in the Gaziantep Organized Industrial Zone of southeast Turkey. Methods: A total of 25 environmental samples (18 soil samples and 7 water samples were taken from The Gaziantep Organized Industrial Zone, in two different seasons (summer and winter. All of the samples were screened for parasites using microscopic examination and culture methods. The parasites were genotyped with polymerase chain reaction and DNA sequencing analysis. Results: The prevalence of soil and water transmitted parasites was found to be positive 52% (13/25 in summer while there is no any parasites in winter. It was found 22.3% (4/18 Acanthamoeba (genotype4, 16.6% (3/18 Ascaris lumbricoides, 11.1% (2/18 Strongoides stercoralis in soil samples and 14.3% (1/7 Acanthamoeba (genotype 4, 42.9% (3/7 Blastocystis (subtype3 in all of water samples. Conclusion: The migratory worker waves have always shaped the ethnic composition and public health problem of the province of Gaziantep. Climate change has the potential to influence prevalence of parasite and our study has shown that increased prevalence of parasite in summer. The global target for the coming years should be to remove the deaths from earth and waterborne parasitic infections in the worker populations. Thus, we prevent the distribution of parasitic infections in our country.

Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages.

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Toshihiko Suzuki

2007-08-01

Full Text Available Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but the precise mechanisms of this activation remain poorly understood. We demonstrate here that caspase-1 activation and IL-1beta processing induced by Shigella are mediated through Ipaf, a cytosolic pattern-recognition receptor of the nucleotide-binding oligomerization domain (NOD-like receptor (NLR family, and the adaptor protein apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC. We also show that Ipaf was critical for pyroptosis, a specialized form of caspase-1-dependent cell death induced in macrophages by bacterial infection, whereas ASC was dispensable. Unlike that observed in Salmonella and Legionella, caspase-1 activation induced by Shigella infection was independent of flagellin. Notably, infection of macrophages with Shigella induced autophagy, which was dramatically increased by the absence of caspase-1 or Ipaf, but not ASC. Autophagy induced by Shigella required an intact bacterial type III secretion system but not VirG protein, a bacterial factor required for autophagy in epithelial-infected cells. Treatment of macrophages with 3-methyladenine, an inhibitor of autophagy, enhanced pyroptosis induced by Shigella infection, suggesting that autophagy protects infected macrophages from pyroptosis. Thus, Ipaf plays a critical role in caspase-1 activation induced by Shigella independently of flagellin. Furthermore, the absence of Ipaf or caspase-1, but not ASC, regulates pyroptosis and the induction of autophagy in Shigella-infected macrophages, providing a novel function for NLR proteins in bacterial-host interactions.

Intestinal parasitic infections among expatriate workers in various occupations in Sharjah, United Arab Emirates.

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Dafalla, Abdelmunim Izzeldin Abdelrahman; Almuhairi, Shaikha Ali Salem Obaid; AlHosani, Mohamed Hassan Jasim; Mohamed, Mira Yousif; Alkous, Mariam Ibrahim Ahmed; AlAzzawi, Mousa Abdelsattar; Abakar, Adam Dawoud; Nour, Bakri Yousif Mohamed; Hasan, Hayder; AbuOdeh, Ra'ed Omar; ElBakri, Ali

2017-12-21

Intestinal parasitic infections are prevalent throughout many countries. This study aimed to determine the prevalence of intestinal parasite carriers among 21,347 expatriate workers, including food handlers and housemaids attending the public health center laboratory in Sharjah, UAE. Stool sample collection was performed throughout the period between January and December 2013. All samples were examined microscopically. Demographic data were also obtained and analyzed. Intestinal parasites were found in 3.3% (708/21,347) of the studied samples (single and multiple infections). Among positive samples, six hundred and eighty-three samples (96.5%) were positive for a single parasite: Giardia lamblia (257; 36.3%) and Entamoeba histolytica/Entamoeba dispar (220; 31.1%), respectively, whereas mono-infections with helminths accounted for 206 (29.1%) of the samples. Infection rates with single worms were: Ascaris lumbricoides (84; 11.9%), Hookworm (34; 4.8%), Trichuris trichiura (33; 4.7%), Taenia spp. (27; 3.81%), Strongyloides stercoralis (13; 1.8%), Hymenolepis nana (13; 1.8%), and Enterobius vermicularis (2; 0.28%), respectively. Infections were significantly associated with gender (x2 = 14.18; p = 0.002) with males as the most commonly infected with both groups of intestinal parasites (protozoa and helminths). A strong statistical association was noted correlating the parasite occurrence with certain nationalities (x2= 49.5, p parasite occurrence and occupation (x2= 15.60; p = 0.029). Multiple infections were not common (3.5% of the positive samples), although one individual (0.14%) had four helminth species, concurrently. These findings emphasized that food handlers with different pathogenic parasitic organisms may pose a significant health risk to the public.

Intestinal Parasitic Infections among Pregnant Women in Venezuela

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2006-01-01

Full Text Available Introduction. Intestinal parasitic infections, especially due to helminths, increase anemia in pregnant women. The results of this are low pregnancy weight gain and IUGR, followed by LBW, with its associated greater risks of infection and higher perinatal mortality rates. For these reasons, in the setting of no large previous studies in Venezuela about this problem, a national multicentric study was conducted. Methods. Pregnant women from nine states were studied, a prenatal evaluation with a coproparasitological study. Univariated and multivariated analyses were made to determine risk factors for intestinal parasitosis and related anemia. Results. During 19 months, 1038 pregnant women were included and evaluated. Intestinal parasitosis was evidenced in 73.9%: A lumbricoides 57.0%, T trichiura 36.0%, G lamblia 14.1%, E hystolitica 12.0%, N americanus 8.1%, E vermicularis 6.3%, S stercoralis 3.3%. Relative risk for anemia in those women with intestinal parasitosis was 2.56 ( P<.01 . Discussion. Intestinal parasitoses could be associated with conditions for development of anemia at pregnancy. These features reflect the need of routine coproparasitological study among pregnant women in rural and endemic zones for intestinal parasites. Further therapeutic and prophylactic protocols are needed. Additional research on pregnant intestinal parasitic infection impact on newborn health is also considered.

Intestinal Parasitic Infections among Pregnant Women in Venezuela

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Rodríguez-Morales, Alfonso J.; Barbella, Rosa A.; Case, Cynthia; Arria, Melissa; Ravelo, Marisela; Perez, Henry; Urdaneta, Oscar; Gervasio, Gloria; Rubio, Nestor; Maldonado, Andrea; Aguilera, Ymora; Viloria, Anna; Blanco, Juan J.; Colina, Magdary; Hernández, Elizabeth; Araujo, Elianet; Cabaniel, Gilberto; Benitez, Jesús; Rifakis, Pedro

2006-01-01

Introduction. Intestinal parasitic infections, especially due to helminths, increase anemia in pregnant women. The results of this are low pregnancy weight gain and IUGR, followed by LBW, with its associated greater risks of infection and higher perinatal mortality rates. For these reasons, in the setting of no large previous studies in Venezuela about this problem, a national multicentric study was conducted. Methods. Pregnant women from nine states were studied, a prenatal evaluation with a coproparasitological study. Univariated and multivariated analyses were made to determine risk factors for intestinal parasitosis and related anemia. Results. During 19 months, 1038 pregnant women were included and evaluated. Intestinal parasitosis was evidenced in 73.9%: A lumbricoides 57.0%, T trichiura 36.0%, G lamblia 14.1%, E hystolitica 12.0%, N americanus 8.1%, E vermicularis 6.3%, S stercoralis 3.3%. Relative risk for anemia in those women with intestinal parasitosis was 2.56 (P Intestinal parasitoses could be associated with conditions for development of anemia at pregnancy. These features reflect the need of routine coproparasitological study among pregnant women in rural and endemic zones for intestinal parasites. Further therapeutic and prophylactic protocols are needed. Additional research on pregnant intestinal parasitic infection impact on newborn health is also considered. PMID:17093349

Secondary Defense Chemicals in Milkweed Reduce Parasite Infection in Monarch Butterflies, Danaus plexippus.

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Gowler, Camden D; Leon, Kristoffer E; Hunter, Mark D; de Roode, Jacobus C

2015-06-01

In tri-trophic systems, herbivores may benefit from their host plants in fighting parasitic infections. Plants can provide parasite resistance in two contrasting ways: either directly, by interfering with the parasite, or indirectly, by increasing herbivore immunity or health. In monarch butterflies, the larval diet of milkweed strongly influences the fitness of a common protozoan parasite. Toxic secondary plant chemicals known as cardenolides correlate strongly with parasite resistance of the host, with greater cardenolide concentrations in the larval diet leading to lower parasite growth. However, milkweed cardenolides may covary with other indices of plant quality including nutrients, and a direct experimental link between cardenolides and parasite performance has not been established. To determine if the anti-parasitic activity of milkweeds is indeed due to secondary chemicals, as opposed to nutrition, we supplemented the diet of infected and uninfected monarch larvae with milkweed latex, which contains cardenolides but no nutrients. Across three experiments, increased dietary cardenolide concentrations reduced parasite growth in infected monarchs, which consequently had longer lifespans. However, uninfected monarchs showed no differences in lifespan across treatments, confirming that cardenolide-containing latex does not increase general health. Our results suggest that cardenolides are a driving force behind plant-derived resistance in this system.

From Parasite Encounter to Infection: Multiple-Scale Drivers of Parasite Richness in a Wild Social Primate Population

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Benavides J. A.; Huchard, E.; Pettorelli, N.; King, A. J.; Brown, M. E.; Archer, C. E.; Appleton, C. C.; Raymond, M.; Cowlishaw, G.

2011-01-01

Host parasite diversity plays a fundamental role in ecological and evolutionary processes, yet the factors that drive it are still poorly understood. A variety of processes, operating across a range of spatial scales, are likely to influence both the probability of parasite encounter and subsequent infection. Here, we explored eight possible determinants of parasite richness, comprising rainfall and temperature at the population level, ranging behavior and home range productivity at the group level, and age, sex, body condition, and social rank at the individual level. We used a unique dataset describing gastrointestinal parasites in a terrestrial subtropical vertebrate (chacma baboons, Papio ursinus), comprising 662 faecal samples from 86 individuals representing all age-sex classes across two groups over two dry seasons in a desert population. Three mixed models were used to identify the most important factor at each of the three spatial scales (population, group, individual); these were then standardised and combined in a single, global, mixed model. Individual age had the strongest influence on parasite richness, in a convex relationship. Parasite richness was also higher in females and animals in poor condition, albeit at a lower order of magnitude than age. Finally, with a further halving of effect size, parasite richness was positively correlated to day range and temperature. These findings indicate that a range of factors influence host parasite richness through both encounter and infection probabilities, but that individual-level processes may be more important than those at the group or population level.

Comparative Evaluation of Permissiveness to Dengue Virus Serotype 2 Infection in Primary Rodent Macrophages

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Jeanette Prada-Arismendy

2012-01-01

Full Text Available Infection with dengue virus presents a broad clinical spectrum, which can range from asymptomatic cases to severe cases that are characterised by haemorrhagic syndrome and/or shock. The reason for such variability remains unknown. This work evaluated the in vitro permissiveness of mouse, rat, hamster and guinea pig macrophages to infection by dengue virus 2 (DENV2. The results established that macrophages derived from the BALB/c mouse strain showed higher permissiveness to DENV2 infection than macrophages from other rodent species, although all rodent species studied had the C820T mutation in the oligoadenylate synthetase 1b gene, indicating no relationship to the different in vitro susceptibilities of mouse cells at this locus. Other molecular mechanisms related to flavivirus susceptibility remain to be explored.

Identification of Francisella novicida mutants that fail to induce prostaglandin E2 synthesis by infected macrophages.

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Matthew Dale Woolard

2013-02-01

Full Text Available Francisella tularensis is the causative agent of tularemia. We have previously shown that infection with F. tularensis Live Vaccine Strain (LVS induces macrophages to synthesize prostaglandin E2 (PGE2. Synthesis of PGE2 by F. tularensis infected macrophages results in decreased T cell proliferation in vitro and increased bacterial survival in vivo. Although we understand some of the biological consequences of F. tularensis induced PGE2 synthesis by macrophages, we do not understand the cellular pathways (neither host nor bacterial that result in up-regulation of the PGE2 biosynthetic pathway in F. tularensis infected macrophages. We took a genetic approach to begin to understand the molecular mechanisms of bacterial induction of PGE2 synthesis from infected macrophages. To identify F. tularensis genes necessary for the induction of PGE2 in primary macrophages, we infected cells with individual mutants from the closely related strain Francisella tularensis subspecies novicida U112 (U112 two allele mutant library. Twenty genes were identified that when disrupted resulted in U112 mutant strains unable to induce the synthesis of PGE2 by infected macrophages. Fourteen of the genes identified are located within the Francisella pathogenicity island (FPI. Genes in the FPI are required for F. tularensis to escape from the phagosome and replicate in the cytosol, which might account for the failure of U112 with transposon insertions within the FPI to induce PGE2. This implies that U112 mutant strains that do not grow intracellularly would also not induce PGE2. We found that U112 clpB::Tn grows within macrophages yet fails to induce PGE2, while U112 pdpA::Tn does not grow yet does induce PGE2. We also found that U112 iglC::Tn neither grows nor induces PGE2. These findings indicate that there is dissociation between intracellular growth and the ability of F. tularensis to induce PGE2 synthesis. These mutants provide a critical entrée into the pathways used

The transcriptome of Legionella pneumophila-infected human monocyte-derived macrophages.

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Christopher T D Price

Full Text Available Legionella pneumophila is an intracellular bacterial pathogen that invades and replicates within alveolar macrophages through injection of ∼ 300 effector proteins by its Dot/Icm type IV translocation apparatus. The bona fide F-box protein, AnkB, is a nutritional virulence effector that triggers macrophages to generate a surplus of amino acids, which is essential for intravacuolar proliferation. Therefore, the ankB mutant represents a novel genetic tool to determine the transcriptional response of human monocyte-derived macrophages (hMDMs to actively replicating L. pneumophila.Here, we utilized total human gene microarrays to determine the global transcriptional response of hMDMs to infection by wild type or the ankB mutant of L. pneumophila. The transcriptomes of hMDMs infected with either actively proliferating wild type or non-replicative ankB mutant bacteria were remarkably similar. The transcriptome of infected hMDMs was predominated by up-regulation of inflammatory pathways (IL-10 anti-inflammatory, interferon signaling and amphoterin signaling, anti-apoptosis, and down-regulation of protein synthesis pathways. In addition, L. pneumophila modulated diverse metabolic pathways, particularly those associated with bio-active lipid metabolism, and SLC amino acid transporters expression.Taken together, the hMDM transcriptional response to L. pneumophila is independent of intra-vacuolar replication of the bacteria and primarily involves modulation of the immune response and metabolic as well as nutritional pathways.

Solute carrier protein family 11 member 1 (Slc11a1) activation efficiently inhibits Leishmania donovani survival in host macrophages.

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Singh, Nisha; Gedda, Mallikarjuna Rao; Tiwari, Neeraj; Singh, Suya P; Bajpai, Surabhi; Singh, Rakesh K

2017-09-01

Visceral leishmaniasis (kala-azar), a life threatening disease caused by L. donovani , is a latent threat to more than 147 million people living in disease endemic South East Asia region of the Indian subcontinent. The therapeutic option to control leishmanial infections are very limited, and at present comprise only two drugs, an antifungal amphotericin B and an antitumor miltefosine, which are also highly vulnerable for parasitic resistance. Therefore, identification and development of alternate control measures is an exigent requirement to control leishmanial infections. In this study, we report that functionally induced expression of solute carrier protein family 11 member 1 ( Slc11a1), a transmembrane divalent cationic transporter recruited on the surface of phagolysosomes after phagocytosis of parasites, effectively inhibits Leishmania donovani growth in host macrophages. Further, the increased Slc11a1 functionality also resulted in increased production of NOx, TNF-α and IL-12 by activated macrophages. The findings of this study signify the importance of interplay between Slc11a1 expression and macrophages activation that can be effectively used to control of Leishmania growth and survival.

Haemosporidian parasite infections in grouse and ptarmigan: Prevalence and genetic diversity of blood parasites in resident Alaskan birds

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Smith, Matthew M.; Van Hemert, Caroline R.; Merizon, Richard

2016-01-01

Projections related to future climate warming indicate the potential for an increase in the distribution and prevalence of blood parasites in northern regions. However, baseline data are lacking for resident avian host species in Alaska. Grouse and ptarmigan occupy a diverse range of habitat types throughout the northern hemisphere and are among the most well-known and important native game birds in North America. Information regarding the prevalence and diversity of haemosporidian parasites in tetraonid species is limited, with few recent studies and an almost complete lack of genetic data. To better understand the genetic diversity of haemosporidian parasites in Alaskan tetraonids and to determine current patterns of geographic range and host specificity, we used molecular methods to screen 459 tissue samples collected from grouse and ptarmigan species across multiple regions of Alaska for infection by Leucocytozoon, Haemoproteus, and Plasmodium blood parasites. Infections were detected in 342 individuals, with overall apparent prevalence of 53% for Leucocytozoon, 21% for Haemoproteus, and 9% for Plasmodium. Parasite prevalence varied by region, with different patterns observed between species groups (grouse versus ptarmigan). Leucocytozoon was more common in ptarmigan, whereas Haemoproteus was more common in grouse. We detected Plasmodium infections in grouse only. Analysis of haemosporidian mitochondrial DNA cytochrome b sequences revealed 23 unique parasite haplotypes, several of which were identical to lineages previously detected in other avian hosts. Phylogenetic analysis showed close relationships between haplotypes from our study and those identified in Alaskan waterfowl for Haemoproteus and Plasmodium parasites. In contrast, Leucocytozoon lineages were structured strongly by host family. Our results provide some of the first genetic data for haemosporidians in grouse and ptarmigan species, and provide an initial baseline on the prevalence and diversity

Correlation between iron deficiency anemia and intestinal parasitic infection in school-age children in Medan

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Darlan, D. M.; Ananda, F. R.; Sari, M. I.; Arrasyid, N. K.; Sari, D. I.

2018-03-01

Anemia is an abnormal hemoglobin concentration in blood that impacts almost 40% school-age children in developing countries. Intestinal parasitic infection, along with malnutrition are contributed to influence absorption, transportation, and metabolism of iron which is the most common etiology of anemia in school-age children. The purpose of this study was to determine whether there is a correlation between iron deficiency anemia (IDA) and parasitic intestinal infection generally and protozoa infection particularly among school-age children in Medan. This was a cross-sectional study conducted from May until October 2016 in primaryschool in Medan and Hamparan Perak, Deli Serdang. Consecutive sampling was used with total 132 samples obtained. Univariate analysis and Bivariate analysis were performed.This study showed the prevalence of IDA was 7.6%, and proportion of parasitic intestinal infection was 26.5% with 19.8% protozoa infection. The correlation between IDA and intestinal parasitic infection was not significant in Chi-Square Test (p-value: 0.089), neither was between IDA and protozoa infection (p-value: 0.287). There was a correlation between MCV, MCH, and anemia with p-valueanemia, parasitic infection, and protozoa infection (p-value>0.05).

Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina infected with SIVmac239

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Tian-Zhang Song

2018-01-01

Full Text Available Parasites can increase infection rates andpathogenicity in immunocompromised humanimmunodeficiency virus (HIV patients. However, invitro studies and epidemiological investigationsalso suggest that parasites might escapeimmunocompromised hosts during HIV infection.Due to the lack of direct evidence from animalexperiments, the effects of parasitic infections onimmunocompromised hosts remain unclear. Here,we detected 14 different parasites in six northernpig-tailed macaques (NPMs before or during the50th week of post-simian immunodeficiency virus(SIV infection by ELISA. The NPMs all carriedparasites before viral injection. At the 50th week afterviral injection, the individuals with negative resultsin parasitic detection (i.e., 08247 and 08287 werecharacterized as the Parasites Exit (PE group, withthe other individuals (i.e., 09203, 09211, 10205, and10225 characterized as the Parasites Remain (PRgroup. Compared with the PR group, the NPMs in thePE group showed higher viral loads, lower CD4+ Tcells counts, and lower CD4/CD8 rates. Additionally,the PE group had higher immune activation andimmune exhaustion of both CD4+ and CD8+ T cells.Pathological observation showed greater injury tothe liver, cecum, colon, spleen, and mesentericlymph nodes in the PE group. This study showedmore seriously compromised immunity in the PEgroup, strongly indicating that parasites might exit animmunocompromised host.

Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina) infected with SIVmac239.

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Song, Tian-Zhang; Zhang, Ming-Xu; Xia, Yu-Jie; Xiao, Yu; Pang, Wei; Zheng, Yong-Tang

2018-01-18

Parasites can increase infection rates and pathogenicity in immunocompromised human immunodeficiency virus (HIV) patients. However, in vitro studies and epidemiological investigations also suggest that parasites might escape immunocompromised hosts during HIV infection. Due to the lack of direct evidence from animal experiments, the effects of parasitic infections on immunocompromised hosts remain unclear. Here, we detected 14 different parasites in six northern pig-tailed macaques (NPMs) before or at the 50th week of simian immunodeficiency virus (SIV) infection by ELISA. The NPMs all carried parasites before viral injection. At the 50th week after viral injection, the individuals with negative results in parasitic detection (i.e., 08247 and 08287) were characterized as the Parasites Exit (PE) group, with the other individuals (i.e., 09203, 09211, 10205, and 10225) characterized as the Parasites Remain (PR) group. Compared with the PR group, the NPMs in the PE group showed higher viral loads, lower CD4 + T cells counts, and lower CD4/CD8 rates. Additionally, the PE group had higher immune activation and immune exhaustion of both CD4 + and CD8 + T cells. Pathological observation showed greater injury to the liver, cecum, colon, spleen, and mesenteric lymph nodes in the PE group. This study showed more seriously compromised immunity in the PE group, strongly indicating that parasites might exit an immunocompromised host.

Intestinal parasitic infections among expatriate workers in various occupations in Sharjah, United Arab Emirates

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Abdelmunim Izzeldin Abdelrahman Dafalla

2017-12-01

Full Text Available ABSTRACT Intestinal parasitic infections are prevalent throughout many countries. This study aimed to determine the prevalence of intestinal parasite carriers among 21,347 expatriate workers, including food handlers and housemaids attending the public health center laboratory in Sharjah, UAE. Stool sample collection was performed throughout the period between January and December 2013. All samples were examined microscopically. Demographic data were also obtained and analyzed. Intestinal parasites were found in 3.3% (708/21,347 of the studied samples (single and multiple infections. Among positive samples, six hundred and eighty-three samples (96.5% were positive for a single parasite: Giardia lamblia (257; 36.3% and Entamoeba histolytica/Entamoeba dispar (220; 31.1%, respectively, whereas mono-infections with helminths accounted for 206 (29.1% of the samples. Infection rates with single worms were: Ascaris lumbricoides (84; 11.9%, Hookworm (34; 4.8%, Trichuris trichiura (33; 4.7%, Taenia spp. (27; 3.81%, Strongyloides stercoralis (13; 1.8%, Hymenolepis nana (13; 1.8%, and Enterobius vermicularis (2; 0.28%, respectively. Infections were significantly associated with gender (x2 = 14.18; p = 0.002 with males as the most commonly infected with both groups of intestinal parasites (protozoa and helminths. A strong statistical association was noted correlating the parasite occurrence with certain nationalities (x2= 49.5, p <0.001. Furthermore, the study has also found a strong statistical correlation between parasite occurrence and occupation (x2= 15.60; p = 0.029. Multiple infections were not common (3.5% of the positive samples, although one individual (0.14% had four helminth species, concurrently. These findings emphasized that food handlers with different pathogenic parasitic organisms may pose a significant health risk to the public.

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X-box binding protein 1 transcription factor.

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Dias-Teixeira, Karina Luiza; Calegari-Silva, Teresa Cristina; dos Santos, Guilherme R R M; Vitorino Dos Santos, José; Lima, Carolina; Medina, Jorge Mansur; Aktas, Bertal Huseyin; Lopes, Ulisses G

2016-04-01

Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR duringLeishmania amazonensisinfection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 μM) increasedL. amazonensisinfectivity in an IFN1-α receptor (IFNAR)-dependent manner. In Western blot assays, we showed thatL. amazonensisactivates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for theIfnbgene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-β expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude thatL. amazonensisactivation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-β expression.-Dias-Teixeira, K. L., Calegari-Silva, T. C., Dos Santos, G. R. R. M., Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The integrated endoplasmic reticulum stress response inLeishmania amazonensismacrophage infection: the role of X-box binding protein 1 transcription factor. © FASEB.

Viable group A streptococci in macrophages during acute soft tissue infection.

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Pontus Thulin

2006-03-01

Full Text Available Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections

Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection.

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2006-01-01

Full Text Available BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis

Association between parasitic infections and tuberculin skin test results in refugees.

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Watts, Nathaniel S; Mizinduko, Mucho M; Barnett, Elizabeth D; White, Laura F; Hochberg, Natasha S

Parasitic infections are known to modulate the immune response necessary for controlling Mycobacterium tuberculosis infection. We sought to investigate species-specific effects of parasite infection on M. tuberculosis infection. As part of the Refugee Health Assessment Program, stool examinations and tuberculin skin testing were performed on refugees seen at Boston Medical Center between 1995 and 2012. Tuberculin skin test (TST) and stool examination data were collected for 6669 refugees; 3349 (50.2%) were TST positive (≥10 mm). Among TST-positive subjects, 176 (5.3%) had helminth infections and 1149 (34.3%) protozoa. After adjusting for sex, age, and country of origin, helminth and protozoan infections were not associated with TST-positivity. When species-specific effects were examined, subjects infected with Trichuris trichiura and Giardia lamblia had reduced odds of TST-positivity (adjusted OR [aOR] 0.65 [95%CI 0.44-0.96; p = 0.03] and aOR 0.79 [95%CI 0.65-0.95, p = 0.01], respectively). Our findings suggest that T. trichiura and G. lamblia may provide protection against M. tuberculosis infection. This study adds to a growing body of literature suggesting that immune response modulation and susceptibility to M. tuberculosis infection is parasite species-dependent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coxsackievirus B4 Can Infect Human Peripheral Blood-Derived Macrophages

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Enagnon Kazali Alidjinou

2015-11-01

Full Text Available Beyond acute infections, group B coxsackieviruses (CVB are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases.

Macrophages facilitate the excystation and differentiation of Toxoplasma gondii sporozoites into tachyzoites following oocyst internalisation.

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Freppel, Wesley; Puech, Pierre-Henri; Ferguson, David J P; Azas, Nadine; Dubey, Jitender P; Dumètre, Aurélien

2016-09-19

Toxoplasma gondii is a common parasite of humans and animals, which is transmitted via oocysts in cat faeces or tissue cysts in contaminated meat. The robust oocyst and sporocyst walls protect the infective sporozoites from deleterious external attacks including disinfectants. Upon oocyst acquisition, these walls lose their integrity to let the sporozoites excyst and invade host cells following a process that remains poorly understood. Given the resistance of the oocyst wall to digestive enzymes and the ability of oocysts to cause parenteral infections, the present study investigated the possible contribution of macrophages in supporting sporozoite excystation following oocyst internalisation. By using single cell micromanipulations, real-time and time-point imaging techniques, we demonstrated that RAW macrophages could interact rapidly with oocysts and engulfed them by remodelling of their actin cytoskeleton. Internalised oocysts were associated to macrophage acidic compartments and showed evidences of wall disruption. Sporozoites were observed in macrophages containing oocyst remnants or in new macrophages, giving rise to dividing tachyzoites. All together, these results highlight an unexpected role of phagocytic cells in processing T. gondii oocysts, in line with non-classical routes of infection, and open new perspectives to identify chemical factors that lead to oocyst wall disruption under physiological conditions.

The landscape of human genes involved in the immune response to parasitic worms

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Fumagalli Matteo

2010-08-01

Full Text Available Abstract Background More than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. Therefore, helminth infections can be regarded as a strong selective pressure. Results Here we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for SNPs that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas. By a genome-wide search we identified 3478 variants that correlate with helminth diversity. These SNPs map to 810 distinct human genes including loci involved in regulatory T cell function and in macrophage activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis of functional relationships among these genes identified complex interaction networks centred around Th2 cytokines. Finally, several genes carrying candidate targets for helminth-driven selective pressure also harbour susceptibility alleles for asthma/allergy or are involved in airway hyper-responsiveness, therefore expanding the known parallelism between these conditions and parasitic infections. Conclusions Our data provide a landscape of human genes that modulate susceptibility to helminths and indicate parasitic worms as one of the major selective forces in humans.

The dynamics of neutrophils in zebrafish (Danio rerio) during infection with the parasite Ichthyophthirius multifiliis

DEFF Research Database (Denmark)

Jørgensen, Louise von Gersdorff

2016-01-01

Ichthyophthirius multifiliis is a ciliated protozoan parasite infecting the skin and gills of freshwater fish. Neutrophils are attracted to the infection sites, as a part of the innate immune response. In this study a transgenic line of zebrafish (Tg(MPO:GFP)i114) with GFP-tagged neutrophils was ...... the infection. Neutrophils interacted directly with the parasites with pseudopod formation projecting towards the pathogen. These results indicate a strong innate immune response immediately following infection and/or a subsequent immune evasion by the parasite....

Practical parasitology courses and infection with intestinal parasites in students.

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Fallahi, Sh; Rostami, A; Mohammadi, M; Ebrahimzadeh, F; Pournia, Y

2016-01-01

Students who are working in research or educational laboratories of parasitology, as well as health care workers providing care for patients, are at the risk of becoming infected with parasites through accidental exposure. The main purpose of this study was to identify potential positive cases of intestinal parasitic infections among students who took practical parasitology courses compared with students who did not take any practical parasitology courses in Lorestan University of Medical Sciences, Khorramabad, Iran, in 2013-2014. A total of 310 subjects from various majors were invited to voluntarily participate in the study. Various demographic data were collected using questionnaires. Three stool samples were collected from each individual on alternate days. Saline wet mounts (SWM), formalin-ether sedimentation test (FEST), Sheather floatation test (SHFT) and trichrome and modified Ziehl-Neelsen staining methods were used to diagnose the presence of intestinal parasites. The prevalence rate of intestinal parasites (IPs) among the students was 11.93%. There was a significant difference between majors in the infection with IPs (Pparasites in the educational course of practical parasitology could occur and must be taken into careful consideration. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Carotenoid-dependent coloration of male American kestrels predicts ability to reduce parasitic infections

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Dawson, Russell D.; Bortolotti, Gary R.

2006-12-01

The signaling function of sexually selected traits, such as carotenoid-dependent avian plumage coloration, has received a great deal of recent attention especially with respect to parasitism and immunocompetence. We argue that parasite-mediated models of sexual selection may have an implicit temporal component that many researchers have ignored. For example, previous studies have demonstrated that carotenoid-dependent traits can signal past parasite exposure, current levels of parasitism, or the ability of individuals to manage parasitic infections in the future. We examined repeated measures of carotenoid-dependent skin color and blood parasitism in American kestrels ( Falco sparverius) to distinguish whether coloration might signal current parasitism or the potential to deal with infections in the future. We found no evidence that coloration was related to current levels of parasitism in either sex. However, coloration of males significantly predicted their response to parasitism; males with bright orange coloration during prelaying, when mate choice is occurring, were more likely than dull yellow males to reduce their levels of infection by the time incubation began. Coloration during prelaying may advertise a male’s health later in the breeding season. For kestrels, the ability to predict future health would be highly beneficial given the male’s role in providing food to his mate and offspring. Coloration of females was not a significant predictor of parasitism in the future, and we provide several possible explanations for this result.

Prevalence and Risk Factors of Intestinal Parasite Infection among Schoolchildren in the Peripheral Highland Regions of Huanuco, Peru.

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Choi, Byungjin; Kim, Bongyoung

2017-10-01

Schoolchildren in developing countries are at greater risk of intestinal parasitic infections. This study aimed to estimate the prevalence and assess the risk factors of intestinal parasite infection among schoolchildren in rural areas of Peru. A volunteer team from the Korea International Cooperation Agency (KOICA) conducted a campaign for parasite eradication called "Chao parasitos" at five schools in the peripheral highland regions of Huanuco in October 2013. The study collected questionnaires and stool samples from children of participating schools. Entamoeba coli , Iodamoeba buschii , and Chilomastix mesnil were classified as nonpathogenic parasites. The overall prevalence of intestinal parasite infection in the students was 100% (185/185). Among them, 25.9% (48/185) were infected only with nonpathogenic parasites whereas 74.1% (137/185) were infected with at least one pathogenic parasite. Ascaris lumbricoides was the most commonly detected (37.3%, 69/185), followed by Giardia lamblia (15.1%, 28/185) and I. buschii (11.9%, 22/185). Among lifestyle practices associated with parasitic infection, the rate of washing hands before meals was significantly lower in the students with pathogenic parasites compared to those with nonpathogenic parasites (77.4%, 106/137 vs. 93.8%, 45/48, p = 0.025). The prevalence of intestinal parasite was 100%. Both personal hygiene and water supply facilities are required to eradicate parasite infection in rural areas of Peru.

Infection of juvenile edible crabs, Cancer pagurus by a haplosporidian-like parasite.

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Thrupp, Tara J; Lynch, Sharon A; Wootton, Emma C; Malham, Shelagh K; Vogan, Claire L; Culloty, Sarah C; Rowley, Andrew F

2013-09-01

This study aimed to examine the pathobiology of a haplosporidian-like infection in juvenile (pre-recruit) edible crabs (Cancer pagurus) from two locations in South West Wales, UK. Infected crabs showed no external symptoms of the disease but dissection revealed an infected and hypertrophic antennal gland. Histological examination showed extensive parasitisation of the antennal gland overlying the hepatopancreas. Heavily infected crabs also showed the presence of parasites with morphological similarities to Haplosporidia in the labyrinth of the antennal gland and in the gills. The spread of the infection from the antennal gland to the gills suggests that these parasites are released into the haemolymph. Attempts to characterise the haplosporidian-like organism using several primers previously shown to amplify members of the phylum Haplosporidia failed. The prevalence of infection in juvenile edible crabs varied throughout the sampling period of November 2011 to July 2012 with the lowest level of ca. 15% in November peaking at 70% in March. This parasite may represent a threat to the sustainability of edible crab fisheries in this region if the damage observed in the antennal gland and gills results in host mortality. The identification of these parasites as members of the phylum Haplosporidia based on morphology alone must be seen as tentative in the absence of sequence data. Copyright © 2013 Elsevier Inc. All rights reserved.

Parasite load in the blood and skin of dogs naturally infected by Leishmania infantum is correlated with their capacity to infect sand fly vectors.

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Borja, Lairton Souza; Sousa, Orlando Marcos Farias de; Solcà, Manuela da Silva; Bastos, Leila Andrade; Bordoni, Marcelo; Magalhães, Jairo Torres; Larangeira, Daniela Farias; Barrouin-Melo, Stella Maria; Fraga, Deborah Bittencourt Mothé; Veras, Patrícia Sampaio Tavares

2016-10-15

The sand fly Lutzomyia longipalpis is primarily responsible for the transmission of visceral leishmaniasis (VL) in the New World, and dogs are considered to be the main urban reservoir of this disease. In order to improve the efficacy of control measures, it is essential to assess the transmission capacity of Leishmania infantum to the sand fly vector by naturally infected dogs. The present study investigated the existence of correlations between canine clinical presentation and the intensity of parasite load in the blood, skin and spleen of naturally infected dogs. In addition, we also attempted to establish correlations between the intensity of parasite load in canine tissue and the parasite load detected in sandflies five days after feeding on naturally infected dogs. A total of 23 dogs were examined and classified according to clinical manifestation of canine VL. Blood samples, splenic aspirate and skin biopsies were collected and parasite DNA was quantified by qPCR. Canine capacity to infect Lu. longipalpis with parasites was evaluated by xenodiagnosis and parasite loads were measured five days after feeding. No significant differences were observed with respect to canine clinical manifestation and the parasite loads detected in the blood, skin and spleen samples obtained from naturally infected dogs. Regardless of clinical canine visceral leishmaniasis (CVL) presentation and the degree of parasite burden, almost half of the dogs successfully infected sandflies with parasites, albeit to a low number of sandflies with correspondingly low parasite loads. Parasite loads in both canine blood and skin were shown to be positively correlated with the canine infectiousness to the sand fly vector, and positive correlations were also observed with respect to these tissues and the sand fly infection rate, as well as the parasite load detected in sandflies following xenodiagnosis. In conclusion, this indicates that parasite loads in both blood and skin can function as

Intestinal Parasitic Infections in Human Immunodeficiency Virus-Infected and Noninfected Persons in a High Human Immunodeficiency Virus Prevalence Region of Cameroon.

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Nkenfou, Céline Nguefeu; Tchameni, Sandrine Mboula; Nkenfou, Carine Nguefeu; Djataou, Patrice; Simo, Ulrich Florian; Nkoum, Alexandre Benjamin; Estrin, William

2017-09-01

The problem of intestinal parasitic infection in human immunodeficiency virus (HIV)-infected people requires careful consideration in the developing world where poor nutrition is associated with poor hygiene and several coinfecting diseases. Studies have addressed this issue in Cameroon, especially in the low HIV prevalence area. The current study was conducted to determine the prevalence of intestinal parasitosis in people living with HIV (PLHIV) in Adamaoua and to identify associated risk factors. Stool and blood specimens from study participants were screened for intestinal parasites and anti-HIV antibodies, respectively. Of 235 participants, 68 (28.9%) were HIV positive, 38 of them on antiretroviral treatment (ART). The overall prevalence of intestinal parasites was 32.3%. Of 68 PLHIV, 32.3% (22/68) were infected with intestinal parasites, compared with 32.3% (54/167) of the HIV-negative patients. Univariate analysis showed no difference between the prevalence of intestinal parasites among PLHIV and HIV-negative patients ( P = 0.69). ART was not associated with the prevalence of intestinal parasites. Multivariate analysis showed that the quality of water and the personal hygiene were the major risk factors associated to intestinal parasitosis. The level of education was associated with HIV serostatus: the higher the level of education, the lower the risk of being infected with HIV ( P = 0.00). PLHIV and the general population should be screened routinely for intestinal parasites and treated if infected.

Experimental Evolution of Mycobacterium tuberculosis in Human Macrophages Results in Low-Frequency Mutations Not Associated with Selective Advantage.

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Valentina Guerrini

Full Text Available Isolates of the human pathogen Mycobacterium tuberculosis recovered from clinical samples exhibit genetic heterogeneity. Such variation may result from the stressful environment encountered by the pathogen inside the macrophage, which is the host cell tubercle bacilli parasitize. To study the evolution of the M. tuberculosis genome during growth inside macrophages, we developed a model of intracellular culture in which bacteria were serially passaged in macrophage-like THP-1 cells for about 80 bacterial generations. Genome sequencing of single bacterial colonies isolated before and after the infection cycles revealed that M. tuberculosis developed mutations at a rate of about 5.7 × 10-9 / bp/ generation, consistent with mutation rates calculated during in vivo infection. Analysis of mutant growth in macrophages and in mice showed that the mutations identified after the cyclic infection conferred no advantage to the mutants relative to wild-type. Furthermore, activity testing of the recombinant protein harboring one of these mutations showed that the presence of the mutation did not affect the enzymatic activity. The serial infection protocol developed in this work to study M. tuberculosis genome microevolution can be applied to exposure to stressors to determine their effect on genome remodeling during intra-macrophage growth.

Parasite infections in nestling red-shouldered hawks (Buteo lineatus) in northeast Wisconsin.

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King, Janet C; Dubay, Shelli A; Huspeni, Todd C; VanLanen, Andrew R; Gerhold, Richard W

2010-06-01

Red-shouldered hawks (Buteo lineatus) are threatened in Wisconsin and long-term data suggest that nest productivity is low in the state for unknown reasons. Our objective was to determine whether red-shouldered hawks in northeast Wisconsin were infected with parasites that could contribute to low nest productivity. We examined nestlings for the presence of Trichomonas gallinae, Protocalliphora avium, and blood parasites in June 2006 and 2007. We did not detect T. gallinae in throat swabs taken from 24 nestlings in 2007. Ear canals of nestlings were parasitized by P. avium larvae in 10 of 11 (91%) nests and in 22 of 24 (92%) nestlings. Larvae were found in higher intensity in 1 ear relative to the other. Leucocytozoon toddi was present in 90.5% (38/42) of the nestlings. At least 1 bird in each nest was infected. Intensity of L. toddi averaged 48.6 +/- 58.3 infected cells per 2,000 erythrocytes (2.4 +/- 2.9%). No other blood parasites were identified.

Molecular appraisal of intestinal parasitic infection in transplant recipients

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Pooja Yadav

2016-01-01

Full Text Available Background & objectives: Diarrhoea is the main clinical manifestation caused by intestinal parasitic infections in patients, with special reference to transplant recipients who require careful consideration to reduce morbidity and mortality. Further, molecular characterization of some important parasites is necessary to delineate the different modes of transmission to consider appropriate management strategies. We undertook this study to investigate the intestinal parasitic infections in transplant recipients with or without diarrhoea, and the genotypes of the isolated parasites were also determined. Methods: Stool samples from 38 transplant recipients comprising 29 post-renal, two liver and seven bone marrow transplant (BMT recipients presenting with diarrhoea and 50 transplant recipients (42 post-renal transplant, eight BMT without diarrhoea were examined for the presence of intestinal parasites by light microscopy using wet mount, modified Ziehl-Neelsen staining for intestinal coccidia and modified trichrome staining for microsporidia. Genotypes of Cryptosporidium species were determined by multilocus genotyping using small subunit ribosomal (SSUrRNA, Cryptosporidium oocyst wall protein (COWP and dihydrofolate reductase (DHFR as the target genes. Assemblage study for Giardia lamblia was performed using triose phosphate isomerase (TPI as the target gene. Samples were also screened for bacterial, fungal and viral pathogens. Results: The parasites that were detected included Cryptosporidium species (21%, 8/38, Cystoisospora (Isospora belli (8%, 3, Cyclospora cayetanensis (5%, 2, G. lamblia (11%, 4, Hymenolepis nana (11%, 4, Strongyloides stercoralis (3%, 1 and Blastocystis hominis (3%, 1. Multilocus genotyping of Cryptosporidium species at SSUrRNA, COWP and DHFR loci could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. All the C. hominis isolates were detected in adult post

Prevalence of intestinal parasitic infections among highland and lowland dwellers in Gamo area, South Ethiopia

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Wegayehu Teklu

2013-02-01

Full Text Available Abstract Background Epidemiological information on the prevalence of intestinal parasitic infections in different regions is a prerequisite to develop appropriate control strategies. Therefore, this present study was conducted to assess the magnitude and pattern of intestinal parasitism in highland and lowland dwellers in Gamo area, South Ethiopia. Methods Community-based cross-sectional study was conducted between September 2010 and July 2011 at Lante, Kolla Shelle, Dorze and Geressie kebeles of Gamo Gofa Zone, South Ethiopia. The study sites and study participants were selected using multistage sampling method. Data were gathered through house-to-house survey. A total of 858 stool specimens were collected and processed using direct wet mount and formol-ether concentration techniques for the presence of parasite. Results Out of the total examined subjects, 342(39.9% were found positive for at least one intestinal parasite. The prevalence of Entamoeba histolytica/dispar was the highest 98(11.4%, followed by Giardia lamblia 91(10.6%, Ascaris lumbricoides 67(7.8%, Strongyloides stercoralis 51(5.9%, hookworm 42(4.9%, Trichuris trichiura 24(2.8%, Taenia species 18(2.1%, Hymenolepis nana 7(0.6% and Schistosoma mansoni 1(0.12%. No statistically significant difference was observed in the prevalence of intestinal parasitic infections among lowland (37.9% and highland dwellers (42.3% (P = 0.185. The prevalence of intestinal parasitic infection was not significantly different among the study sites but it was relatively higher in Geressie (42.8% than other kebeles. Sex was not associated with parasitic infections (P = 0.481. No statistically significant difference of infection was observed among the age groups (P = 0.228 but it was higher in reproductive age group. Conclusions The high prevalence of intestinal parasitic infections among the lowland and highland dwellers in Gamo area indicated that parasitic infections are important public

Prevalence of intestinal parasitic infections among highland and lowland dwellers in Gamo area, South Ethiopia.

Science.gov (United States)

Wegayehu, Teklu; Tsalla, Tsegaye; Seifu, Belete; Teklu, Takele

2013-02-18

Epidemiological information on the prevalence of intestinal parasitic infections in different regions is a prerequisite to develop appropriate control strategies. Therefore, this present study was conducted to assess the magnitude and pattern of intestinal parasitism in highland and lowland dwellers in Gamo area, South Ethiopia. Community-based cross-sectional study was conducted between September 2010 and July 2011 at Lante, Kolla Shelle, Dorze and Geressie kebeles of Gamo Gofa Zone, South Ethiopia. The study sites and study participants were selected using multistage sampling method. Data were gathered through house-to-house survey. A total of 858 stool specimens were collected and processed using direct wet mount and formol-ether concentration techniques for the presence of parasite. Out of the total examined subjects, 342(39.9%) were found positive for at least one intestinal parasite. The prevalence of Entamoeba histolytica/dispar was the highest 98(11.4%), followed by Giardia lamblia 91(10.6%), Ascaris lumbricoides 67(7.8%), Strongyloides stercoralis 51(5.9%), hookworm 42(4.9%), Trichuris trichiura 24(2.8%), Taenia species 18(2.1%), Hymenolepis nana 7(0.6%) and Schistosoma mansoni 1(0.12%). No statistically significant difference was observed in the prevalence of intestinal parasitic infections among lowland (37.9%) and highland dwellers (42.3%) (P = 0.185). The prevalence of intestinal parasitic infection was not significantly different among the study sites but it was relatively higher in Geressie (42.8%) than other kebeles. Sex was not associated with parasitic infections (P = 0.481). No statistically significant difference of infection was observed among the age groups (P = 0.228) but it was higher in reproductive age group. The high prevalence of intestinal parasitic infections among the lowland and highland dwellers in Gamo area indicated that parasitic infections are important public health problems. Thus, infection control measures and the

Detection of circulating parasite-derived microRNAs in filarial infections.

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Lucienne Tritten

2014-07-01

Full Text Available Filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. Applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. As a first step, we investigated the presence of circulating miRNAs released by filarial nematodes into the host bloodstream. miRNA deep-sequencing combined with bioinformatics revealed over 200 mature miRNA sequences of potential nematode origin in Dirofilaria immitis-infected dog plasma in two independent analyses, and 21 in Onchocerca volvulus-infected human serum. Total RNA obtained from D. immitis-infected dog plasma was subjected to stem-loop RT-qPCR assays targeting two detected miRNA candidates, miR-71 and miR-34. Additionally, Brugia pahangi-infected dog samples were included in the analysis, as these miRNAs were previously detected in extracts prepared from this species. The presence of miR-71 and miR-34 discriminated infected samples (both species from uninfected samples, in which no specific miRNA amplification occurred. However, absolute miRNA copy numbers were not significantly correlated with microfilaraemia for either parasite. This may be due to the imprecision of mf counts to estimate infection intensity or to miRNA contributions from the unknown number of adult worms present. Nonetheless, parasite-derived circulating miRNAs are found in plasma or serum even for those species that do not live in the bloodstream.

Knowledge based assessment of intestinal parasitic Infections ...

African Journals Online (AJOL)

There is an apparent lack of information on the risk and clinical symptoms of Intestinal Parasitic Infections (IPIs) among students attending boarding secondary schools in Ebonyi State, Nigeria. This questionnaire-based survey attempts to assess some behavioural habits, possible risk factor(s) as well as clinical symptoms ...

Intestinal parasite infections in symptomatic children attending hospital in Siem Reap, Cambodia.

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Moore, Catrin E; Nget, Phot; Saroeun, Mao; Kuong, Suy; Chanthou, Seng; Kumar, Varun; Bousfield, Rachel; Nader, Johanna; Bailey, J Wendi; Beeching, Nicholas J; Day, Nicholas P; Parry, Christopher M

2015-01-01

Infections with helminths and other intestinal parasites are an important but neglected problem in children in developing countries. Accurate surveys of intestinal parasites in children inform empirical treatment regimens and can assess the impact of school based drug treatment programmes. There is limited information on this topic in Cambodia. In a prospective study of intestinal parasites in symptomatic children attending Angkor Hospital for Children, Siem Reap, Cambodia, April-June 2012, samples were examined by microscopy of a direct and concentrated fecal sample. Two culture methods for hookworm and Strongyloides stercoralis were employed when sufficient sample was received. Demographic, clinical and epidemiological data were collected. We studied 970 samples from 865 children. The median (inter-quartile range) age of the children was 5.4 (1.9-9.2) years, 54% were male. The proportion of children with abdominal pain was 66.8%, diarrhea 34.9%, anemia 12.7% and malnutrition 7.4%. 458 parasitic infections were detected in 340 (39.3%) children. The most common parasites using all methods of detection were hookworm (14.3%), Strongyloides stercoralis (11.6%) and Giardia lamblia (11.2%). Giardia lamblia was most common in children aged 1-5 years, hookworm and Strongyloides stercoralis were more common with increasing age. Hookworm, Strongloides stercoralis and Giardia lamblia were more common in children living outside of Siem Reap town. In a multivariate logistic regression increasing age was associated with all three infections, defecating in the forest for hookworm infection, the presence of cattle for S. stercoralis and not using soap for handwashing for G. lamblia. This study confirms the importance of intestinal parasitic infections in symptomatic Cambodian children and the need for adequate facilities for laboratory diagnosis together with education to improve personal hygiene and sanitation.

Intestinal parasite infections in symptomatic children attending hospital in Siem Reap, Cambodia.

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Catrin E Moore

Full Text Available Infections with helminths and other intestinal parasites are an important but neglected problem in children in developing countries. Accurate surveys of intestinal parasites in children inform empirical treatment regimens and can assess the impact of school based drug treatment programmes. There is limited information on this topic in Cambodia.In a prospective study of intestinal parasites in symptomatic children attending Angkor Hospital for Children, Siem Reap, Cambodia, April-June 2012, samples were examined by microscopy of a direct and concentrated fecal sample. Two culture methods for hookworm and Strongyloides stercoralis were employed when sufficient sample was received. Demographic, clinical and epidemiological data were collected.We studied 970 samples from 865 children. The median (inter-quartile range age of the children was 5.4 (1.9-9.2 years, 54% were male. The proportion of children with abdominal pain was 66.8%, diarrhea 34.9%, anemia 12.7% and malnutrition 7.4%. 458 parasitic infections were detected in 340 (39.3% children. The most common parasites using all methods of detection were hookworm (14.3%, Strongyloides stercoralis (11.6% and Giardia lamblia (11.2%. Giardia lamblia was most common in children aged 1-5 years, hookworm and Strongyloides stercoralis were more common with increasing age. Hookworm, Strongloides stercoralis and Giardia lamblia were more common in children living outside of Siem Reap town. In a multivariate logistic regression increasing age was associated with all three infections, defecating in the forest for hookworm infection, the presence of cattle for S. stercoralis and not using soap for handwashing for G. lamblia.This study confirms the importance of intestinal parasitic infections in symptomatic Cambodian children and the need for adequate facilities for laboratory diagnosis together with education to improve personal hygiene and sanitation.

Cytopathology of parasitic dermatitis in dogs.

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Sood, N K; Mekkib, Berhanu; Singla, L D; Gupta, K

2012-04-01

Out of 44 cases of dermatitis in dogs, 11 cases of parasitic origin were analyzed by cytopathology. Histopathologic examination of punch biopsies was also done for correlation with cytologic findings. Sarcoptic dermatitis was recorded in six cases, wherein, besides sarcoptic mites, neutrophils, macrophages, and plasma cells and keratinizing epithelial cells were also seen. Hematology revealed a relative neutrophilia and mild eosinophilia. Four cases of severe and generalized demodicosis complicated with bacteria and/or Malassezia sp. infection were also recorded. Histopathologically numerous Demodex sp. mites in varying stage of maturation were found damaging the hair follicles along with associated pathological changes and foreign body granulomas in one case. In addition, flea allergy dermatitis was also observed in one dog. In nutshell, cytology was found to be unequivocally effective in diagnosing parasitic dermatitis.

High prevalence of diarrhoegenic intestinal parasite infections among non-ART HIV patients in Fitche Hospital, Ethiopia.

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Adamu, Haileeyesus; Wegayehu, Teklu; Petros, Beyene

2013-01-01

HIV infection has been modifying both the epidemiology and outcome of parasite infections. Hence, this study was undertaken to determine the prevalence of Cryptosporidium and other intestinal parasite infections among HIV positives with and without Antiretroviral Treatment(ART) and its association with CD4+ T-cell count. A cross-sectional study was conducted at Fitche hospital focusing on HIV positives who came to hospital for follow-ups. A total of 378 HIV positive persons with and without ART participated in the study. Data on socio-demographic factors and diarrhoea status were obtained by interviewing all 214 with ART and 164 without ART. Stool samples were collected from all patients and examined for intestinal parasites using direct, formol-ether and modified acid-fast staining techniques. The prevalence of intestinal parasite infections in this study was significantly higher among HIV positive persons not on ART. Specifically, the rate of infection with Cryptosporidium species, Blastocystis spp., Giardia lamblia, and Entamoeba histolytica/E. dispar were higher, particularly in those with CD4+ T-cell counts less than 200 cells/µL. Fifty seven percent of the study participants were on ART. Out of these 164/378 (43%) of the non-ART study participants were infected with at least one intestinal parasite species. Significant association was observed between lower CD4+ T-cell count (parasites were significantly more prevalent in HIV positive non-ART patients. HIV infection increased the risk of having Cryptosporidium and other intestinal parasites and diarrhoea. Therefore, raising HIV positive's immune status and screening for intestinal parasites is important. This study showed that patients who are taking ART had a lower prevalence of diarrhoea causing parasites and Cryptosporidium suggesting that ART through improvement of immune status of the patients may have contributed to controlling diarrhoea-causing parasites in HIV positive patients.

The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies.

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Ben-Ami, F; Rigaud, T; Ebert, D

2011-06-01

In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less-virulent parasite may protect the host against the more-virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood-infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less-virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Targeting channels and transporters in protozoan parasite infections

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Meier, Anna; Erler, Holger; Beitz, Eric

2018-03-01

Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e. channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

Parasite prevalence, infection intensity and richness in an endangered population, the Atlantic-Gaspésie caribou.

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Turgeon, Geneviève; Kutz, Susan J; Lejeune, Manigandan; St-Laurent, Martin-Hugues; Pelletier, Fanie

2018-04-01

The Atlantic-Gaspésie caribou ( Rangifer tarandus caribou ) population is a small isolated relict herd considered endangered according to the Canadian Species at Risk Act (SARA). This population has low recruitment and survival rates but the potential role of parasites on individual fitness is unknown. In this context, we explored the parasite status of this population with the aim of 1) assessing the occurrence and intensity of parasite infections and the spatial, temporal and individual variations, 2) quantifying parasite richness and investigating factors such as sex and host body condition that may be associated with this variable and 3) evaluating the effects of parasite infections on survival in the Atlantic-Gaspésie caribou population. We examined fecal samples from 32 animals captured in 2013-2014 for eggs, oocysts and larvae of parasites and detected 7 parasite species: dorsal-spined larvae protostrongylids, presumably Parelaphostrongylus andersoni based on PCR identification of a subset, Nematodirus odocoilei and other unidentified Strongyles, Trichuris sp., Capillaria sp., Moniezia sp. and Eimeria sp. For each caribou, mean parasite species richness was 1.8 ± 1.1 (SD). Sex, body condition, year and capture location did not explain parasite prevalence, intensity of infection or richness except for intensity of infection of Capillaria sp. that was positively influenced by body condition. Parasites did not influence survival although mortality was higher for males than for females. We suggest that the relatively low and common gastrointestinal and protostrongylid parasite infections will not be a short-term threat leading to extinction.

Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

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Matthew Calverley

Full Text Available Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM. However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

The interrelation between intestinal parasites and latent TB infections among newly resettled refugees in Texas.

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Board, Amy R; Suzuki, Sumihiro

2016-01-01

Previous research has documented that parasite infection may increase vulnerability to TB among certain at risk populations. The purpose of this study was to identify whether an association exists between latent tuberculosis infection (LTBI) and intestinal parasite infection among newly resettled refugees in Texas while controlling for additional effects of region of origin, age and sex. Data for all refugees screened for both TB and intestinal parasites between January 2010 and mid-October 2013 were obtained from the Texas Refugee Health Screening Program and were analyzed using logistic regression. A total of 9860 refugees were included. In multivariable logistic regression analysis, pathogenic and non-pathogenic intestinal parasite infections yielded statistically significant reduced odds of LTBI. However, when individual parasite species were analyzed, hookworm infection indicated statistically significant increased odds of LTBI (OR 1.674, CI: 1.126-2.488). A positive association exists between hookworm infection and LTBI in newly arrived refugees to Texas. More research is needed to assess the nature and extent of these associations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Parasitic helminth infections in native sheep (Mehraban in Hamedan, Iran

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Jamal Gharekhani

2015-06-01

Full Text Available Sheep play an important role in national economy and social economy in rural areas in Iran. The main goal of this study was to investigate the fauna and frequency of parasitic helminth infections prevalent in native sheep in Hamedan, western Iran. From April 2010 to March 2011, the gastrointestinal and respiratory tracts of 100-sheep were examined using conventional parasitological methods. The overall infection rate was found as 69%. No infection was found in esophagus and rumens. Parabronema skerjabini (22% and Ostertagia circumcincta (1% were recorded as the maximum and minimum cases for the presence of nematode, respectively. On the other hand, the most dominant of trematode and cestode were Fasciola hepatica (13% and Monezia expansa (13%, respectively. The highest infection rate was reported in summer (84%. The prevalence of helminth infection was varied among gender, seasons and age groups. In conclusion, this is the first report of parasitic helminth infections in sheep in Hamedan province in western Iran. Our results provide baseline information for the future studies.

Characteristic features of intracellular pathogenic Leptospira in infected murine macrophages.

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Toma, Claudia; Okura, Nobuhiko; Takayama, Chitoshi; Suzuki, Toshihiko

2011-11-01

Leptospira interrogans is a spirochaete responsible for a zoonotic disease known as leptospirosis. Leptospires are able to penetrate the abraded skin and mucous membranes and rapidly disseminate to target organs such as the liver, lungs and kidneys. How this pathogen escape from innate immune cells and spread to target organs remains poorly understood. In this paper, the intracellular trafficking undertaken by non-pathogenic Leptospira biflexa and pathogenic L. interrogans in mouse bone marrow-derived macrophages was compared. The delayed in the clearance of L. interrogans was observed. Furthermore, the acquisition of lysosomal markers by L. interrogans-containing phagosomes lagged behind that of L. biflexa-containing phagosomes, and although bone marrow-derived macrophages could degrade L. biflexa as well as L. interrogans, a population of L. interrogans was able to survive and replicate. Intact leptospires were found within vacuoles at 24 h post infection, suggesting that bacterial replication occurs within a membrane-bound compartment. In contrast, L. biflexa were completely degraded at 24 h post infection. Furthermore, L. interrogans but not L. biflexa, were released to the extracellular milieu. These results suggest that pathogenic leptospires are able to survive, replicate and exit from mouse macrophages, enabling their eventual spread to target organs. © 2011 Blackwell Publishing Ltd.

Decreased expression of liver X receptor-α in macrophages infected with Chlamydia pneumoniae in human atherosclerotic arteries in situ.

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Bobryshev, Yuri V; Orekhov, Alexander N; Killingsworth, Murray C; Lu, Jinhua

2011-01-01

In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells. Copyright © 2011 S. Karger AG, Basel.

Alternative states and population crashes in a resource-susceptible-infected model for planktonic parasites and hosts

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Gerla, D.J.; Gsell, A.S.; Kooi, B.W.; Ibelings, B.W.; Van Donk, E.; Mooij, W.M.

2013-01-01

1. Despite the strong impact parasites can have, only few models of phytoplankton ecology or aquatic food webs have specifically included parasitism. 2. Here, we provide a susceptible-infected model for a diatom-chytrid host–parasite system that explicitly includes nutrients, infected and uninfected

Biochemical and morphological changes associated with macrophages and osteoclasts when challenged with infection - biomed 2011.

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Wiggers, Erin Callie; Johnson, William; Tucci, Michelle; Benghuzzi, Hamed

2011-01-01

Osteomyelitis is a bacterial infection of the bone that occurs frequently as a complication of open fractures and various kinds of orthopedic surgery. This infection can often lead to more extensive surgeries and even death of the patient. In animal models of osteomyelitis, the site of infection by Staphylococcus aureus was observed to have high numbers of both macrophages and osteoclasts, both of which may contribute to large amounts of osteolysis and tissue damage. In order to evaluate the immune response in both types of cells, two cells lines, a macrophage cell line and a macrophage cell line stimulated to become osteoclasts by the addition of receptor activator of nuclear-factor B (RANKL), were exposed to lipopolysaccharides, opsonized S. aureus, and unopsonized S. aureus. The results showed that both cell types activated a biochemical cascade that included the release of cytokines and nitric oxide associated with cell damage and death in response to infection. However, macrophages and osteoclasts differed in response magnitude, most likely due to differences in cell-membrane receptors. This data supports the growing body of research that links the immune and skeletal systems. Further understanding of biochemical pathways shared by the two systems could lead to significant advances in the treatment of osteomyelitis and the success of prostheses.

Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV in Ugandan women

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Ndibazza Juliet

2011-09-01

Full Text Available Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods and antibodies against Kaposi's sarcoma herpesvirus (KSHV, measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01, hookworm (67% vs 56% p = 0.001 and Mansonella perstans (69% vs 59% p = 0.05; seroprevalence increased with increasing intensity of hookworm infection (p Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

Cryptosporidium and other intestinal parasitic infections among HIV patients in southern Ethiopia: significance of improved HIV-related care.

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Shimelis, Techalew; Tassachew, Yayehyirad; Lambiyo, Tariku

2016-05-10

Intestinal parasitic infections are known to cause gastroenteritis, leading to higher morbidity and mortality, particularly in people living with HIV/AIDS. This study aimed to determine the prevalence of Cryptosporidium and other intestinal parasitic infections among HIV patients receiving care at a hospital in Ethiopia where previous available baseline data helps assess if improved HIV-related care has reduced infection rates. A cross-sectional study was conducted at Hawassa University Hospital in southern Ethiopia from May, 2013 to March, 2014. A consecutive sample of 491 HIV- infected patients with diarrhea or a CD4 T cell count intestinal parasites. The study was approved by the Institutional Review Board of the College of Medicine and Health Sciences, Hawassa University. Physicians managed participants found to be infected with any pathogenic intestinal parasite. The overall prevalence of intestinal parasitic infections among the study population was 35.8 %. The most prevalent parasites were Cryptosporidium (13.2 %), followed by Entamoeba histolytica/dispar (10.2 %), and Giardia lamblia (7.9 %). The rate of single and multiple infections were 25.5 and 10.3 %, respectively. Patients with a CD4 T cell count intestinal parasitic infection or cryptosporidiosis compared to those with counts ≥ 200 cells/μl, but with some type of diarrhea. The study shows high prevalence of intestinal parasitic infections in the study population. However, the results in the current report are significantly lower compared to previous findings in the same hospital. The observed lower infection rate is encouraging and supports the need to strengthen and sustain the existing intervention measures in order to further reduce intestinal parasitic infections in people living with HIV/AIDS.

The bacterial parasite Pasteuria ramosa is not killed if it fails to infect: implications for coevolution.

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King, Kayla C; Auld, Stuart K J R; Wilson, Philip J; James, Janna; Little, Tom J

2013-02-01

Strong selection on parasites, as well as on hosts, is crucial for fueling coevolutionary dynamics. Selection will be especially strong if parasites that encounter resistant hosts are destroyed and diluted from the local environment. We tested whether spores of the bacterial parasite Pasteuria ramosa were passed through the gut (the route of infection) of their host, Daphnia magna, and whether passaged spores remained viable for a "second chance" at infecting a new host. In particular, we tested if this viability (estimated via infectivity) depended on host genotype, whether or not the genotype was susceptible, and on initial parasite dose. Our results show that Pasteuria spores generally remain viable after passage through both susceptible and resistant Daphnia. Furthermore, these spores remained infectious even after being frozen for several weeks. If parasites can get a second chance at infecting hosts in the wild, selection for infection success in the first instance will be reduced. This could also weaken reciprocal selection on hosts and slow the coevolutionary process.

Parasite prevalence, infection intensity and richness in an endangered population, the Atlantic-Gaspésie caribou

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Geneviève Turgeon

2018-04-01

Full Text Available The Atlantic-Gaspésie caribou (Rangifer tarandus caribou population is a small isolated relict herd considered endangered according to the Canadian Species at Risk Act (SARA. This population has low recruitment and survival rates but the potential role of parasites on individual fitness is unknown. In this context, we explored the parasite status of this population with the aim of 1 assessing the occurrence and intensity of parasite infections and the spatial, temporal and individual variations, 2 quantifying parasite richness and investigating factors such as sex and host body condition that may be associated with this variable and 3 evaluating the effects of parasite infections on survival in the Atlantic-Gaspésie caribou population. We examined fecal samples from 32 animals captured in 2013–2014 for eggs, oocysts and larvae of parasites and detected 7 parasite species: dorsal-spined larvae protostrongylids, presumably Parelaphostrongylus andersoni based on PCR identification of a subset, Nematodirus odocoilei and other unidentified Strongyles, Trichuris sp., Capillaria sp., Moniezia sp. and Eimeria sp. For each caribou, mean parasite species richness was 1.8 ± 1.1 (SD. Sex, body condition, year and capture location did not explain parasite prevalence, intensity of infection or richness except for intensity of infection of Capillaria sp. that was positively influenced by body condition. Parasites did not influence survival although mortality was higher for males than for females. We suggest that the relatively low and common gastrointestinal and protostrongylid parasite infections will not be a short-term threat leading to extinction. Keywords: Capillaria, Eimeria, Moniezia, Nematodirinae, Parelaphostrongylus andersoni, Rangifer tarandus

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

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Tapas K. Nayak

2017-01-01

Full Text Available Chikungunya virus (CHIKV infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6 MHC-I/II and B7.2 (CD86 were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.

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Nayak, Tapas K; Mamidi, Prabhudutta; Kumar, Abhishek; Singh, Laishram Pradeep K; Sahoo, Subhransu S; Chattopadhyay, Soma; Chattopadhyay, Subhasis

2017-01-06

Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

Mini-FLOTAC, an innovative direct diagnostic technique for intestinal parasitic infections: experience from the field.

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Barda, Beatrice Divina; Rinaldi, Laura; Ianniello, Davide; Zepherine, Henry; Salvo, Fulvio; Sadutshang, Tsetan; Cringoli, Giuseppe; Clementi, Massimo; Albonico, Marco

2013-01-01

Soil-transmitted helminths and intestinal protozoa infection are widespread in developing countries, yet an accurate diagnosis is rarely performed. The aim of this study was to evaluate the recently developed mini-FLOTAC method and to compare with currently more widely used techniques for the diagnosis of intestinal parasitic infections in different settings. The study was carried out in Dharamsala, Himachal Pradesh, India, and in Bukumbi, Tanzania. A total of 180 pupils from two primary schools had their stool analyzed (n = 80 in Dharamsala and n = 100 in Bukumbi) for intestinal parasitic infections with three diagnostic methods: direct fecal smear, formol-ether concentration method (FECM) and mini-FLOTAC. Overall, 72% of the pupils were positive for any intestinal parasitic infection, 24% carried dual infections and 11% three infections or more. The most frequently encountered intestinal parasites were Entamoeba coli, Entamoeba histolytica/dispar, Giardia intestinalis, hookworm, (and Schistosoma mansoni, in Tanzania). Statistically significant differences were found in the detection of parasitic infections among the three methods: mini-FLOTAC was the most sensitive method for helminth infections (90% mini-FLOTAC, 60% FECM, and 30% direct fecal smear), whereas FECM was most sensitive for intestinal protozoa infections (88% FECM, 70% direct fecal smear, and 68% mini-FLOTAC). We present the first experiences with the mini-FLOTAC for the diagnosis of intestinal helminths and protozoa. Our results suggest that it is a valid, sensitive and potentially low-cost alternative technique that could be used in resource-limited settings--particularly for helminth diagnosis.

C–C Chemokines Released by Lipopolysaccharide (LPS)-stimulated Human Macrophages Suppress HIV-1 Infection in Both Macrophages and T Cells

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Verani, Alessia; Scarlatti, Gabriella; Comar, Manola; Tresoldi, Eleonora; Polo, Simona; Giacca, Mauro; Lusso, Paolo; Siccardi, Antonio G.; Vercelli, Donata

1997-01-01

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C–C chemokines (RANTES, MIP-1α, and MIP-1β) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C–C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C–C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes. PMID:9120386

Cross-species infection trials reveal cryptic parasite varieties and a putative polymorphism shared among host species.

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Luijckx, Pepijn; Duneau, David; Andras, Jason P; Ebert, Dieter

2014-02-01

A parasite's host range can have important consequences for ecological and evolutionary processes but can be difficult to infer. Successful infection depends on the outcome of multiple steps and only some steps of the infection process may be critical in determining a parasites host range. To test this hypothesis, we investigated the host range of the bacterium Pasteuria ramosa, a Daphnia parasite, and determined the parasites success in different stages of the infection process. Multiple genotypes of Daphnia pulex, Daphnia longispina and Daphnia magna were tested with four Pasteuria genotypes using infection trials and an assay that determines the ability of the parasite to attach to the hosts esophagus. We find that attachment is not specific to host species but is specific to host genotype. This may suggest that alleles on the locus controlling attachment are shared among different host species that diverged 100 million year. However, in our trials, Pasteuria was never able to reproduce in nonnative host species, suggesting that Pasteuria infecting different host species are different varieties, each with a narrow host range. Our approach highlights the explanatory power of dissecting the steps of the infection process and resolves potentially conflicting reports on parasite host ranges. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Nuclear techniques in the control of parasitic infections

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Mulligan, W.

1976-01-01

The development of radiation-attenuated vaccines against economically important parasitic diseases of farm animals has met with mixed success. Examples are presented ranging from the highly effective and much used commercial vaccine against cattle lungworm to the almost completely unsuccessful attempts to immunize sheep against liver fluke. The results presented emphasize that this approach is likely to be successful only if there is evidence of a strong degree of acquired immunity to the natural infection. The extension of immunological control to those systems where the parasite provokes only a modest resistance by the host will probably depend on a much greater understanding of the mechanism of the immune response. Such fundamental studies are likely to rely heavily on nuclear techniques, e.g. in the labelling of antigens, antibodies and parasites with radioactive isotopes. (author)

High prevalence of diarrhoegenic intestinal parasite infections among non-ART HIV patients in Fitche Hospital, Ethiopia.

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Haileeyesus Adamu

Full Text Available BACKGROUND: HIV infection has been modifying both the epidemiology and outcome of parasite infections. Hence, this study was undertaken to determine the prevalence of Cryptosporidium and other intestinal parasite infections among HIV positives with and without Antiretroviral Treatment(ART and its association with CD4+ T-cell count. METHODS: A cross-sectional study was conducted at Fitche hospital focusing on HIV positives who came to hospital for follow-ups. A total of 378 HIV positive persons with and without ART participated in the study. Data on socio-demographic factors and diarrhoea status were obtained by interviewing all 214 with ART and 164 without ART. Stool samples were collected from all patients and examined for intestinal parasites using direct, formol-ether and modified acid-fast staining techniques. RESULTS: The prevalence of intestinal parasite infections in this study was significantly higher among HIV positive persons not on ART. Specifically, the rate of infection with Cryptosporidium species, Blastocystis spp., Giardia lamblia, and Entamoeba histolytica/E. dispar were higher, particularly in those with CD4+ T-cell counts less than 200 cells/µL. Fifty seven percent of the study participants were on ART. Out of these 164/378 (43% of the non-ART study participants were infected with at least one intestinal parasite species. Significant association was observed between lower CD4+ T-cell count (<200 cells/µL and the prevalence of Cryptosporidium spp. and Blastocystis spp. The two parasites were significantly more prevalent in HIV positive non-ART patients. CONCLUSION: HIV infection increased the risk of having Cryptosporidium and other intestinal parasites and diarrhoea. Therefore, raising HIV positive's immune status and screening for intestinal parasites is important. This study showed that patients who are taking ART had a lower prevalence of diarrhoea causing parasites and Cryptosporidium suggesting that ART through

Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells.

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Danelishvili, Lia; McGarvey, Jeffery; Li, Yong-Jun; Bermudez, Luiz E

2003-09-01

Mycobacterium tuberculosis interacts with macrophages and epithelial cells in the alveolar space of the lung, where it is able to invade and replicate in both cell types. M. tuberculosis-associated cytotoxicity to these cells has been well documented, but the mechanisms of host cell death are not well understood. We examined the induction of apoptosis and necrosis of human macrophages (U937) and type II alveolar epithelial cells (A549) by virulent (H37Rv) and attenuated (H37Ra) M. tuberculosis strains. Apoptosis was determined by both enzyme-linked immunosorbent assay (ELISA) and TdT-mediated dUTP nick end labelling (TUNEL) assay, whereas necrosis was evaluated by the release of lactate dehydrogenase (LDH). Both virulent and attenuated M. tuberculosis induced apoptosis in macrophages; however, the attenuated strain resulted in significantly more apoptosis than the virulent strain after 5 days of infection. In contrast, cytotoxicity of alveolar cells was the result of necrosis, but not apoptosis. Although infection with M. tuberculosis strains resulted in apoptosis of 14% of the cells on the monolayer, cell death associated with necrosis was observed in 59% of alveolar epithelial cells after 5 days of infection. Infection with M. tuberculosis suppressed apoptosis of alveolar epithelial cells induced by the kinase inhibitor, staurosporine. Because our findings suggest that M. tuberculosis can modulate the apoptotic response of macrophages and epithelial cells, we carried out an apoptosis pathway-specific cDNA microarray analysis of human macrophages and alveolar epithelial cells. Whereas the inhibitors of apoptosis, bcl-2 and Rb, were upregulated over 2.5-fold in infected (48 h) alveolar epithelial cells, the proapoptotic genes, bad and bax, were downregulated. The opposite was observed when U937 macrophages were infected with M. tuberculosis. Upon infection of alveolar epithelial cells with M. tuberculosis, the generation of apoptosis, as determined by the

In vitro and in vivo efficacy of ether lipid edelfosine against Leishmania spp. and SbV-resistant parasites.

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Rubén E Varela-M

Full Text Available BACKGROUND: The leishmaniases are a complex of neglected tropical diseases caused by more than 20 Leishmania parasite species, for which available therapeutic arsenal is scarce and unsatisfactory. Pentavalent antimonials (SbV are currently the first-line pharmacologic therapy for leishmaniasis worldwide, but resistance to these compounds is increasingly reported. Alkyl-lysophospoholipid analogs (ALPs constitute a family of compounds with antileishmanial activity, and one of its members, miltefosine, has been approved as the first oral treatment for visceral and cutaneous leishmaniasis. However, its clinical use can be challenged by less impressive efficiency in patients infected with some Leishmania species, including L. braziliensis and L. mexicana, and by proneness to develop drug resistance in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We found that ALPs ranked edelfosine>perifosine>miltefosine>erucylphosphocholine for their antileishmanial activity and capacity to promote apoptosis-like parasitic cell death in promastigote and amastigote forms of distinct Leishmania spp., as assessed by proliferation and flow cytometry assays. Effective antileishmanial ALP concentrations were dependent on both the parasite species and their development stage. Edelfosine accumulated in and killed intracellular Leishmania parasites within macrophages. In vivo antileishmanial activity was demonstrated following oral treatment with edelfosine of mice and hamsters infected with L. major, L. panamensis or L. braziliensis, without any significant side-effect. Edelfosine also killed SbV-resistant Leishmania parasites in in vitro and in vivo assays, and required longer incubation times than miltefosine to generate drug resistance. CONCLUSIONS/SIGNIFICANCE: Our data reveal that edelfosine is the most potent ALP in killing different Leishmania spp., and it is less prone to lead to drug resistance development than miltefosine. Edelfosine is effective in killing Leishmania

CK2 Secreted by Leishmania braziliensis Mediates Macrophage Association Invasion: A Comparative Study between Virulent and Avirulent Promastigotes

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Ana Madeira Brito Zylbersztejn

2015-01-01

Full Text Available CK2 is a protein kinase distributed in different compartments of Leishmania braziliensis: an externally oriented ecto-CK2, an intracellular CK2, and a secreted CK2. This latter form is constitutively secreted from the parasite (CsCK2, but such secretion may be highly enhanced by the association of specific molecules, including enzyme substrates, which lead to a higher enzymatic activity, called inductively secreted CK2 (IsCK2. Here, we examined the influence of secreted CK2 (sCK2 activity on the infectivity of a virulent L. braziliensis strain. The virulent strain presented 121-fold higher total CK2 activity than those found in an avirulent strain. The use of specific CK2 inhibitors (TBB, DRB, or heparin inhibited virulent parasite growth, whereas no effect was observed in the avirulent parasites. When these inhibitors were added to the interaction assays between the virulent L. braziliensis strain and macrophages, association index was drastically inhibited. Polyamines enhanced sCK2 activity and increased the association index between parasites and macrophages. Finally, sCK2 and the supernatant of the virulent strain increased the association index between the avirulent strain and macrophages, which was inhibited by TBB. Thus, the kinase enzyme CK2 seems to be important to invasion mechanisms of L. braziliensis.

CD14-dependent monocyte isolation enhances phagocytosis of listeria monocytogenes by proinflammatory, GM-CSF-derived macrophages.

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Caroline Neu

Full Text Available Macrophages are an important line of defence against invading pathogens. Human macrophages derived by different methods were tested for their suitability as models to investigate Listeria monocytogenes (Lm infection and compared to macrophage-like THP-1 cells. Human primary monocytes were isolated by either positive or negative immunomagnetic selection and differentiated in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF or macrophage colony-stimulating factor (M-CSF into pro- or anti-inflammatory macrophages, respectively. Regardless of the isolation method, GM-CSF-derived macrophages (GM-Mφ stained positive for CD206 and M-CSF-derived macrophages (M-Mφ for CD163. THP-1 cells did not express CD206 or CD163 following incubation with PMA, M- or GM-CSF alone or in combination. Upon infection with Lm, all primary macrophages showed good survival at high multiplicities of infection whereas viability of THP-1 was severely reduced even at lower bacterial numbers. M-Mφ generally showed high phagocytosis of Lm. Strikingly, phagocytosis of Lm by GM-Mφ was markedly influenced by the method used for isolation of monocytes. GM-Mφ derived from negatively isolated monocytes showed low phagocytosis of Lm whereas GM-Mφ generated from positively selected monocytes displayed high phagocytosis of Lm. Moreover, incubation with CD14 antibody was sufficient to enhance phagocytosis of Lm by GM-Mφ generated from negatively isolated monocytes. By contrast, non-specific phagocytosis of latex beads by GM-Mφ was not influenced by treatment with CD14 antibody. Furthermore, phagocytosis of Lactococcus lactis, Escherichia coli, human cytomegalovirus and the protozoan parasite Leishmania major by GM-Mφ was not enhanced upon treatment with CD14 antibody indicating that this effect is specific for Lm. Based on these observations, we propose macrophages derived by ex vivo differentiation of negatively selected human primary monocytes as the most

LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania

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González-Rey, Elena; Delgado, Mario; Castanys, Santiago; Pérez-Victoria, José M.; Gamarro, Francisco

2013-01-01

Leishmaniasis is a neglected disease produced by the intracellular protozoan parasite Leishmania. In the present study, we show that LABCG2, a new ATP-binding cassette half-transporter (ABCG subfamily) from Leishmania, is involved in parasite virulence. Down-regulation of LABCG2 function upon expression of an inactive mutant version of this half-transporter (LABCG2K/M) is shown to reduce the translocation of short-chain analogues of phosphatidylserine (PS). This dominant-negative phenotype is specific for the headgroup of the phospholipid, as the movement of phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine or sphingomyelin is not affected. In addition, promastigotes expressing LABCG2K/M expose less endogenous PS in the stationary phase than control parasites. Transient exposure of PS at the outer leaflet of the plasma membrane is known to be one of the mechanisms used by Leishmania to infect macrophages and to silence their immune response. Stationary phase/metacyclic promastigotes expressing LABCG2K/M are less infective for macrophages and show decreased pathogenesis in a mouse model of cutaneous leishmaniasis. Thus, mice infected with parasites expressing LABCG2K/M did not develop any lesion and showed significantly lower inflammation and parasite burden than mice infected with control parasites. Our results indicate that LABCG2 function is required for the externalization of PS in Leishmania promastigotes, a process that is involved in the virulence of the parasite. PMID:23638200

The Risk of Chronic Gastrointestinal Disorders Following Acute Infection with Intestinal Parasites

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Jason Blitz

2018-01-01

Full Text Available Background: Infectious gastroenteritis (IGE is caused by numerous bacterial, viral, and parasitic pathogens. A history of IGE has been shown in previous studies to increase the risk of developing chronic gastrointestinal disorders and other chronic conditions. As bacteria and viruses represent the majority of pathogen-specific causes of IGE, post-infectious studies have primarily focused on these organisms. The objective of this study was to investigate an association between a history of parasite-associated IGE and the subsequent development of chronic post-infectious gastrointestinal and non-gastrointestinal disorders in a military population.Methods: International Classification of Diseases, 9th Revision Clinical Modification (ICD-9-CM diagnostic coding data for primary exposures and outcomes were obtained for a retrospective cohort study of active component military personnel from 1998 to 2013. Exposed subjects consisted of individuals with documented infection with one of ten parasitic pathogens. Unexposed subjects were matched to exposed subjects on demographic and operational deployment history parameters. Adjusted odds ratios (aORs were estimated using logistic regression for several chronic disorders previously shown to be associated with a history of IGE.Results: A total of 896 subjects with a parasitic exposure were matched to 3681 unexposed subjects for multivariate regression analysis. Individuals infected with Balantidium coli, Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus/Ancylostoma duodenale, and Taenia spp. had higher aOR for development of several chronic gastrointestinal disorders when compared with unexposed subjects after controlling for various covariates.Conclusion: We found that parasite-associated enteric infection increases the risk of development of post-infectious chronic gastrointestinal disorders in a military population. These results require confirmation in similar populations and in the

Analysis of the bovine monocyte-derived macrophage response to Mycobacterium avium subspecies paratuberculosis infection using RNA-seq

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Maura E Casey

2015-02-01

Full Text Available Johne’s disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP, is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne’s disease. Here we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a six-hour infection time course with non-infected controls. We observed 245 and 574 differentially expressed genes in MAP-infected versus non-infected control samples (adjusted P value ≤ 0.05 at 2 and 6 hours post-infection, respectively. Functional analyses of these differentially expressed genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the IL-10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix® microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection.

Playing hide-and-seek with host macrophages through the use of mycobacterial cell envelope phthiocerol dimycocerosates and phenolic glycolipids

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Ainhoa eARBUES

2014-12-01

Full Text Available Mycobacterial pathogens, including Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB, have evolved a remarkable ability to evade the immune system in order to survive and to colonize the host. Among the most important evasion strategies is the capacity of these bacilli to parasitize host macrophages, since these are major effector cells against intracellular pathogens that can be used as long-term cellular reservoirs. Mycobacterial pathogens employ an array of virulence factors that manipulate macrophage function to survive and establish infection. Until recently, however, the role of mycobacterial cell envelope lipids as virulence factors in macrophage subversion has remained elusive. Here, we will address exclusively the proposed role for phthiocerol dimycocerosates (DIM in the modulation of the resident macrophage response and that of phenolic glycolipids (PGL in the regulation of the recruitment and phenotype of incoming macrophage precursors to the site of infection. We will provide a unique perspective of potential additional functions for these lipids, and highlight obstacles and opportunities to further understand their role in the pathogenesis of TB and other mycobacterial diseases.

Blood and milk polymorphonuclear leukocyte and monocyte/macrophage functions in naturally caprine arthritis encephalitis virus infection in dairy goats.

Science.gov (United States)

Santos, Bruna Parapinski; Souza, Fernando Nogueira; Blagitz, Maiara Garcia; Batista, Camila Freitas; Bertagnon, Heloísa Godoi; Diniz, Soraia Araújo; Silva, Marcos Xavier; Haddad, João Paulo Amaral; Della Libera, Alice Maria Melville Paiva

2017-06-01

The exact influence of caprine arthritis encephalitis virus (CAEV) infection on blood and milk polymorphonuclear leukocytes (PMNLs) and monocyte/macrophages of goats remains unclear. Thus, the present study sought to explore the blood and milk PMNL and monocyte/macrophage functions in naturally CAEV-infected goats. The present study used 18 healthy Saanen goats that were segregated according to sera test outcomes into serologically CAEV negative (n=8; 14 halves) and positive (n=10; 14 halves) groups. All milk samples from mammary halves with milk bacteriologically positive outcomes, somatic cell count ≥2×10 6 cellsmL -1 , and abnormal secretions in the strip cup test were excluded. We evaluated the percentage of blood and milk PMNLs and monocyte/macrophages, the viability of PMNLs and monocyte/macrophages, the levels of intracellular reactive oxygen species (ROS) and the nonopsonized phagocytosis of Staphylococcus aureus and Escherichia coli by flow cytometry. In the present study, a higher percentage of milk macrophages (CD14 + ) and milk polymorphonuclear leukocytes undergoing late apoptosis or necrosis (Annexin-V + /Propidium iodide + ) was observed in CAEV-infected goats; we did not find any further alterations in blood and milk PMNL and monocyte/macrophage functions. Thus, regarding our results, the goats naturally infected with CAEV did not reveal pronounced dysfunctions in blood and milk polymorphonuclear leukocytes and monocytes/macrophages. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential expression of miRNAs by macrophages infected with virulent and avirulent Mycobacterium tuberculosis.

Science.gov (United States)

Das, Kishore; Saikolappan, Sankaralingam; Dhandayuthapani, Subramanian

2013-12-01

MicroRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate a wide range of biological processes that include cellular differentiation, development, immunity and apoptosis. There is a growing body of evidences that bacteria modulate immune responses by altering the expression of host miRNAs. Since macrophages are immune cells associated with innate and adaptive immunity, we investigated whether Mycobacterium tuberculosis infection affects miRNAs of macrophages. THP-1 macrophages infected with virulent (H37Rv) and avirulent (H37Ra) strains of M. tuberculosis were analyzed for changes in miRNAs' expression using microarray. This revealed that nine miRNA genes (miR-30a, miR-30e, miR-155, miR-1275, miR-3665, miR-3178, miR-4484, miR-4668-5p and miR-4497) were differentially expressed between THP-1cells infected with M. tuberculosis H37Rv and M. tuberculosis H37Ra strains. Additional characterization of these genes is likely to provide insights into their role in the pathogenesis of tuberculosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Epidemiological assessment of intestinal parasitic infections in dogs at animal shelter in Veracruz, Mexico

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Cosme Alvarado-Esquivel

2015-01-01

Conclusions: A high prevalence of intestinal parasites was found in the dogs studied. This suggests that the environment is highly contaminated with intestinal parasites. Preventive and therapeutic measures should be taken against infection with intestinal parasites in dogs in this region.

HIV and parasitic co-infections in tuberculosis patients

DEFF Research Database (Denmark)

Range, N.; Magnussen, Pascal; Mugomela, A.

2007-01-01

A cross-sectional study was conducted in Mwanza, Tanzania, to determine the burden of HIV and parasitic co-infections among patients who were confirmed or suspected cases of pulmonary tuberculosis (PTB). Of the 655 patients investigated, 532 (81.2%) had been confirmed as PTB cases, by microscopy...

Host density and competency determine the effects of host diversity on trematode parasite infection.

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Jeremy M Wojdak

Full Text Available Variation in host species composition can dramatically alter parasite transmission in natural communities. Whether diverse host communities dilute or amplify parasite transmission is thought to depend critically on species traits, particularly on how hosts affect each other's densities, and their relative competency as hosts. Here we studied a community of potential hosts and/or decoys (i.e. non-competent hosts for two trematode parasite species, Echinostoma trivolvis and Ribeiroia ondatrae, which commonly infect wildlife across North America. We manipulated the density of a focal host (green frog tadpoles, Rana clamitans, in concert with manipulating the diversity of alternative species, to simulate communities where alternative species either (1 replace the focal host species so that the total number of individuals remains constant (substitution or (2 add to total host density (addition. For E. trivolvis, we found that total parasite transmission remained roughly equal (or perhaps decreased slightly when alternative species replaced focal host individuals, but parasite transmission was higher when alternative species were added to a community without replacing focal host individuals. Given the alternative species were roughly equal in competency, these results are consistent with current theory. Remarkably, both total tadpole and per-capita tadpole infection intensity by E. trivolvis increased with increasing intraspecific host density. For R. ondatrae, alternative species did not function as effective decoys or hosts for parasite infective stages, and the diversity and density treatments did not produce clear changes in parasite transmission, although high tank to tank variation in R. ondatrae infection could have obscured patterns.

The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection

OpenAIRE

Huijben, Silvie; Sim, Derek G.; Nelson, William, A.; Read, Andrew F.

2011-01-01

Malaria infections normally consist of more than one clonally-replicating lineage. Within-host interactions between sensitive and resistant parasites can have profound effects on the evolution of drug resistance. Here, using the Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of resistance are affected by the number of co-infecting strains competing with a resistant clone. We found strong competitive suppression of resistant parasites in untreated infections and...

Analysis of a summary network of co-infection in humans reveals that parasites interact most via shared resources

OpenAIRE

Griffiths, Emily C; Pedersen, Amy B; Fenton, Andy; Petchey, Owen L

2014-01-01

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three l...

Trichinella inflammatory myopathy: host or parasite strategy?

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Chiumiento Lorena

2011-03-01

Full Text Available Abstract The parasitic nematode Trichinella has a special relation with muscle, because of its unique intracellular localization in the skeletal muscle cell, completely devoted in morphology and biochemistry to become the parasite protective niche, otherwise called the nurse cell. The long-lasting muscle infection of Trichinella exhibits a strong interplay with the host immune response, mainly characterized by a Th2 phenotype. The aim of this review is to illustrate the role of the Th2 host immune response at the muscle level during trichinellosis in different experimental models, such as knock-out or immuno-modulated mice. In particular, in knock-out mice a crucial role of IL-10 is evident for the regulation of inflammation intensity. The muscular host immune response to Trichinella is partially regulated by the intestinal phase of the parasite which emphasizes the intensity of the following muscle inflammation compared with animals infected by synchronized injections of newborn larvae. In eosinophil-ablated mice such as PHIL and GATA-- animals it was observed that there was an increased NOS2 expression in macrophages, driven by higher IFN-γ release, thus responsible for muscle larva damage. Besides modulation of the intestinal stage of the infection, using recombinant IL-12, increases the muscular parasite burden delaying adult worm expulsion from the intestine. Furthermore, a Th1 adjuvant of bacterial origin called Helicobacter pylori neutrophil activating protein (HP-NAP, administered during the intestinal phase of trichinellosis, alters the Th2 dependent response at muscle level. All these data from the literature delineate then a mutual adaptation between parasite and host immune response in order to achieve a strategic compromise between two evolutionary forces pointed towards the survival of both species.

Involvement of Pro-Inflammatory Macrophages in Liver Pathology of Pirital Virus-Infected Syrian Hamsters

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Corey L. Campbell

2018-05-01

Full Text Available New World arenaviruses cause fatal hemorrhagic disease in South America. Pirital virus (PIRV, a mammarenavirus hosted by Alston’s cotton rat (Sigmodon alstoni, causes a disease in Syrian golden hamsters (Mesocricetus auratus (biosafety level-3, BSL-3 that has many pathologic similarities to the South American hemorrhagic fevers (BSL-4 and, thus, is considered among the best small-animal models for human arenavirus disease. Here, we extend in greater detail previously described clinical and pathological findings in Syrian hamsters and provide evidence for a pro-inflammatory macrophage response during PIRV infection. The liver was the principal target organ of the disease, and signs of Kupffer cell involvement were identified in mortally infected hamster histopathology data. Differential expression analysis of liver mRNA revealed signatures of the pro-inflammatory response, hematologic dysregulation, interferon pathway and other host response pathways, including 17 key transcripts that were also reported in two non-human primate (NHP arenavirus liver-infection models, representing both Old and New World mammarenavirus infections. Although antigen presentation may differ among rodent and NHP species, key hemostatic and innate immune-response components showed expression parallels. Signatures of pro-inflammatory macrophage involvement in PIRV-infected livers included enrichment of Ifng, Nfkb2, Stat1, Irf1, Klf6, Il1b, Cxcl10, and Cxcl11 transcripts. Together, these data indicate that pro-inflammatory macrophage M1 responses likely contribute to the pathogenesis of acute PIRV infection.

A novel approach to parasite population genetics: experimental infection reveals geographic differentiation, recombination and host-mediated population structure in Pasteuria ramosa, a bacterial parasite of Daphnia.

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Andras, J P; Ebert, D

2013-02-01

The population structure of parasites is central to the ecology and evolution of host-parasite systems. Here, we investigate the population genetics of Pasteuria ramosa, a bacterial parasite of Daphnia. We used natural P. ramosa spore banks from the sediments of two geographically well-separated ponds to experimentally infect a panel of Daphnia magna host clones whose resistance phenotypes were previously known. In this way, we were able to assess the population structure of P. ramosa based on geography, host resistance phenotype and host genotype. Overall, genetic diversity of P. ramosa was high, and nearly all infected D. magna hosted more than one parasite haplotype. On the basis of the observation of recombinant haplotypes and relatively low levels of linkage disequilibrium, we conclude that P. ramosa engages in substantial recombination. Isolates were strongly differentiated by pond, indicating that gene flow is spatially restricted. Pasteuria ramosa isolates within one pond were segregated completely based on the resistance phenotype of the host-a result that, to our knowledge, has not been previously reported for a nonhuman parasite. To assess the comparability of experimental infections with natural P. ramosa isolates, we examined the population structure of naturally infected D. magna native to one of the two source ponds. We found that experimental and natural infections of the same host resistance phenotype from the same source pond were indistinguishable, indicating that experimental infections provide a means to representatively sample the diversity of P. ramosa while reducing the sampling bias often associated with studies of parasite epidemics. These results expand our knowledge of this model parasite, provide important context for the large existing body of research on this system and will guide the design of future studies of this host-parasite system. © 2012 Blackwell Publishing Ltd.

Global Dynamics of HIV Infection of CD4+ T Cells and Macrophages

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A. M. Elaiw

2013-01-01

Full Text Available We study the global dynamics of an HIV infection model describing the interaction of the HIV with CD4+ T cells and macrophages. The incidence rate of virus infection and the growth rate of the uninfected CD4+ T cells and macrophages are given by general functions. We have incorporated two types of distributed delays into the model to account for the time delay between the time the uninfected cells are contacted by the virus particle and the time for the emission of infectious (matures virus particles. We have established a set of conditions which are sufficient for the global stability of the steady states of the model. Using Lyapunov functionals and LaSalle's invariant principle, we have proven that if the basic reproduction number R0 is less than or equal to unity, then the uninfected steady state is globally asymptotically stable (GAS, and if the infected steady state exists, then it is GAS.

Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection.

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Veras, Patrícia Sampaio Tavares; Bezerra de Menezes, Juliana Perrone

2016-08-19

Leishmania is a protozoan parasite that causes a wide range of different clinical manifestations in mammalian hosts. It is a major public health risk on different continents and represents one of the most important neglected diseases. Due to the high toxicity of the drugs currently used, and in the light of increasing drug resistance, there is a critical need to develop new drugs and vaccines to control Leishmania infection. Over the past few years, proteomics has become an important tool to understand the underlying biology of Leishmania parasites and host interaction. The large-scale study of proteins, both in parasites and within the host in response to infection, can accelerate the discovery of new therapeutic targets. By studying the proteomes of host cells and tissues infected with Leishmania, as well as changes in protein profiles among promastigotes and amastigotes, scientists hope to better understand the biology involved in the parasite survival and the host-parasite interaction. This review demonstrates the feasibility of proteomics as an approach to identify new proteins involved in Leishmania differentiation and intracellular survival.

Anaemia, Nutritional Status and Parasitic Infection among Preschool ...

African Journals Online (AJOL)

Objective: This study was carried out to determine the packed cell volume nutritional status and parasitic infection among preschool children living in rural villages. Subjects and Methods: A total of 116 preschool children in nine villages formed the population for this study. The preschool children were studied using ...

Geospatial distribution of intestinal parasitic infections in Rio de Janeiro (Brazil) and its association with social determinants.

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Faria, Clarissa Perez; Zanini, Graziela Maria; Dias, Gisele Silva; da Silva, Sidnei; de Freitas, Marcelo Bessa; Almendra, Ricardo; Santana, Paula; Sousa, Maria do Céu

2017-03-01

Intestinal parasitic infections remain among the most common infectious diseases worldwide. This study aimed to estimate their prevalence and provide a detailed analysis of geographical distribution of intestinal parasites in the metropolitan region of Rio de Janeiro, considering demographic, socio-economic, and epidemiological contextual factors. The cross-section survey was conducted among individuals attending the Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ, RJ) during the period from April 2012 to February 2015. Stool samples were collected and processed by sedimentation, flotation, Kato-Katz, Baermann-Moraes and Graham methods, iron haematoxylin staining and safranin staining. Of the 3245 individuals analysed, 569 (17.5%) were infected with at least one parasite. The most common protozoa were Endolimax nana (28.8%), Entamoeba coli (14.8%), Complex Entamoeba histolytica/Entamoeba dispar (13.5%), Blastocystis hominis (12.7%), and Giardia lamblia (8.1%). Strongyloides stercoralis (4.3%), Schistosoma mansoni (3.3%), Ascaris lumbricoides (1.6%), and hookworms (1.5%) were the most frequent helminths. There was a high frequency of contamination by protozoa (87%), and multiple infections were observed in 141 participants (24.8%). A positive association between age (young children) and gender (male) with intestinal parasites was observed. Geospatial distribution of the detected intestinal parasitic infections was not random or homogeneous, but was influenced by socioeconomic conditions (through the material deprivation index (MDI)). Participants classified in the highest levels of deprivation had higher risk of having intestinal parasites. This study provides the first epidemiological information on the prevalence and distribution of intestinal parasitic infections in the Rio de Janeiro metropolitan area. Intestinal parasites, especially protozoa, are highly prevalent, indicating that parasitic infections are still a serious public health problem

Geospatial distribution of intestinal parasitic infections in Rio de Janeiro (Brazil) and its association with social determinants

Science.gov (United States)

Faria, Clarissa Perez; Zanini, Graziela Maria; Dias, Gisele Silva; da Silva, Sidnei; de Freitas, Marcelo Bessa; Almendra, Ricardo; Santana, Paula; Sousa, Maria do Céu

2017-01-01

Background Intestinal parasitic infections remain among the most common infectious diseases worldwide. This study aimed to estimate their prevalence and provide a detailed analysis of geographical distribution of intestinal parasites in the metropolitan region of Rio de Janeiro, considering demographic, socio-economic, and epidemiological contextual factors. Methods/Principal findings The cross-section survey was conducted among individuals attending the Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ, RJ) during the period from April 2012 to February 2015. Stool samples were collected and processed by sedimentation, flotation, Kato-Katz, Baermann-Moraes and Graham methods, iron haematoxylin staining and safranin staining. Of the 3245 individuals analysed, 569 (17.5%) were infected with at least one parasite. The most common protozoa were Endolimax nana (28.8%), Entamoeba coli (14.8%), Complex Entamoeba histolytica/Entamoeba dispar (13.5%), Blastocystis hominis (12.7%), and Giardia lamblia (8.1%). Strongyloides stercoralis (4.3%), Schistosoma mansoni (3.3%), Ascaris lumbricoides (1.6%), and hookworms (1.5%) were the most frequent helminths. There was a high frequency of contamination by protozoa (87%), and multiple infections were observed in 141 participants (24.8%). A positive association between age (young children) and gender (male) with intestinal parasites was observed. Geospatial distribution of the detected intestinal parasitic infections was not random or homogeneous, but was influenced by socioeconomic conditions (through the material deprivation index (MDI)). Participants classified in the highest levels of deprivation had higher risk of having intestinal parasites. Conclusions/Significance This study provides the first epidemiological information on the prevalence and distribution of intestinal parasitic infections in the Rio de Janeiro metropolitan area. Intestinal parasites, especially protozoa, are highly prevalent, indicating that

Biodiversity and systematics of apicomplexan parasites infecting South African leopard and hinged tortoises

OpenAIRE

2010-01-01

M.Sc. Research into blood protozoans (haematozoans) infecting African tortoises is scanty with only a few records published, many during the early part of the last century. Little research had been done on the blood parasites of tortoises examined in this study namely, Kinixys lobatsiana, K. belliana belliana, K. natalensis, Geochelone pardalis pardalis, G. pardalis babcocki and Chersina angulata. The study therefore aimed to: 1) examine apicomplexan haematozoan parasites infecting several...

Extracellular traps are associated with human and mouse neutrophil and macrophage mediated killing of larval Strongyloides stercoralis.

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Bonne-Année, Sandra; Kerepesi, Laura A; Hess, Jessica A; Wesolowski, Jordan; Paumet, Fabienne; Lok, James B; Nolan, Thomas J; Abraham, David

2014-06-01

Neutrophils are multifaceted cells that are often the immune system's first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed that NETs trapped but did not kill larvae. Induction of NETs was essential for larval killing by human but not murine neutrophils and macrophages in vitro. In mice, extracellular traps were induced following infection with S. stercoralis larvae and were present in the microenvironment of worms being killed in vivo. These findings demonstrate that NETs ensnare the parasite facilitating larval killing by cells of the immune system. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

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Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

2014-01-01

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

Biophysics of malarial parasite exit from infected erythrocytes.

Science.gov (United States)

Chandramohanadas, Rajesh; Park, YongKeun; Lui, Lena; Li, Ang; Quinn, David; Liew, Kingsley; Diez-Silva, Monica; Sung, Yongjin; Dao, Ming; Lim, Chwee Teck; Preiser, Peter Rainer; Suresh, Subra

2011-01-01

Upon infection and development within human erythrocytes, P. falciparum induces alterations to the infected RBC morphology and bio-mechanical properties to eventually rupture the host cells through parasitic and host derived proteases of cysteine and serine families. We used previously reported broad-spectrum inhibitors (E64d, EGTA-AM and chymostatin) to inhibit these proteases and impede rupture to analyze mechanical signatures associated with parasite escape. Treatment of late-stage iRBCs with E64d and EGTA-AM prevented rupture, resulted in no major RBC cytoskeletal reconfiguration but altered schizont morphology followed by dramatic re-distribution of three-dimensional refractive index (3D-RI) within the iRBC. These phenotypes demonstrated several-fold increased iRBC membrane flickering. In contrast, chymostatin treatment showed no 3D-RI changes and caused elevated fluctuations solely within the parasitophorous vacuole. We show that E64d and EGTA-AM supported PV breakdown and the resulting elevated fluctuations followed non-Gaussian pattern that resulted from direct merozoite impingement against the iRBC membrane. Optical trapping experiments highlighted reduced deformability of the iRBC membranes upon rupture-arrest, more specifically in the treatments that facilitated PV breakdown. Taken together, our experiments provide novel mechanistic interpretations on the role of parasitophorous vacuole in maintaining the spherical schizont morphology, the impact of PV breakdown on iRBC membrane fluctuations leading to eventual parasite escape and the evolution of membrane stiffness properties of host cells in which merozoites were irreversibly trapped, recourse to protease inhibitors. These findings provide a comprehensive, previously unavailable, body of information on the combined effects of biochemical and biophysical factors on parasite egress from iRBCs.

Epidemiology of infections with intestinal parasites and human immunodeficiency virus (HIV) among sugar-estate residents in Ethiopia

NARCIS (Netherlands)

Fontanet, A. L.; Sahlu, T.; Rinke de Wit, T.; Messele, T.; Masho, W.; Woldemichael, T.; Yeneneh, H.; Coutinho, R. A.

2000-01-01

Intestinal parasitic infections could play an important role in the progression of infection with human immunodeficiency virus (HIV), by further disturbing the immune system whilst it is already engaged in the fight against HIV. HIV and intestinal parasitic infections were investigated in 1239,

PREVALENCE OF PARASITIC INFECTION IN BUFFALO CALVES IN JKHADAGZAI, DISTRICT DIR

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M, Azam. M. M, Siddiqui and G. Habib

2002-04-01

Full Text Available Prevalence of ecto and endo-parasites of buffalo calves was investigated in 50 buffalo farms in Khadagzai area of district Dir. N.W.F.P. Province. Faecal examination of calves (n = 118: age ≤ 1 year revealed that 64.41% of the calves were positive for internal parasites. The worm load significantly varied (P<0.05 among the farms and was the highest (1600-3600 EPG in 2%, moderate (800-1600 EPG in 22%, low (200-800 EPG in 34% and negligible (less than 200 EPG in 42% farms. Among the calves examined 50.84% had the worm load of 200-800 EPG and 13.56% calves showed the worm load of 800-1600 EPG. , The highest worm load (1600-3600 EPG was observed only in 0.85% of the calves. Six species of nematodes and one specie of trematodes were identified. No cestode infection was encountered during the study. The incidence of Trichostrongylus species was 21.19% followed by Trichuris (9.32%. Haemonchus (8.47%, Strongyloides papillosus (5.93%, Ostertagia (5.08%. Toxocara vitulurum (1 .70%. Fasciola (5.93% and mixed infections (6.78%. Intestinal protozoan infection was recorded in 72% of the calves. Majority of the calves (85% had mixed infection of Coccidia and Amoeba and the remaining 15% calves were found infected with Coccidia only. A total of 5.93% of the calves studied were found positive for ecto-parasites. The prevalence of ticks, lice, mites and mixed infection was 5.08, 34.75, 11.86 and 4.24% respectively in the surveyed calves.

Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.

Science.gov (United States)

Rothchild, Alissa C; Stowell, Britni; Goyal, Girija; Nunes-Alves, Cláudio; Yang, Qianting; Papavinasasundaram, Kadamba; Sassetti, Christopher M; Dranoff, Glenn; Chen, Xinchun; Lee, Jinhee; Behar, Samuel M

2017-10-24

Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF -/- ) are highly susceptible to infection with Mycobacterium tuberculosis , and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T cells also produce GM-CSF during M. tuberculosis infection. Early during infection, nonconventional iNKT cells and γδ T cells are the main source of GM-CSF, a role subsequently assumed by conventional CD4 + T cells as the infection progresses. M. tuberculosis -specific T cells producing GM-CSF are also detected in the peripheral blood of infected people. Under conditions where nonhematopoietic production of GM-CSF is deficient, T cell production of GM-CSF is protective and required for control of M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated protection in settings where GM-CSF is produced by other cell types. Finally, using an in vitro macrophage infection model, we demonstrate that GM-CSF inhibition of M. tuberculosis growth requires the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Thus, we identified GM-CSF production as a novel T cell effector function. These findings suggest that a strategy augmenting T cell production of GM-CSF could enhance host resistance against M. tuberculosis IMPORTANCE Mycobacterium tuberculosis is the bacterium that causes tuberculosis, the leading cause of death by any infection worldwide. T cells are critical components of the immune

Challenges in the management of intraocular parasitic infections

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Ashish Mitra

2015-01-01

Full Text Available Parasitic worms in eye is something which is not very uncommon these days. People who eat undercooked food and have pets at home are at more risk to have parasitic infections. Chemoparalysis has been reported in literature using either viscoelastics or preservative free lidocaine (intracamerally to paralyze the worms that help in retrieval, but still one can face tricky situations while managing such conditions. Importance lies in the management of such cases as it can be really challenging at times and no report exists in the literature which mentions the importance of topical lidocaine along with viscoelastics or preservative free lidocaine for retrieval of the worm.

Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS

Energy Technology Data Exchange (ETDEWEB)

Watson, R.R.; Prabhala, R.H.; Darban, H.R.; Yahya, M.D.; Smith, T.L.

1988-01-01

The number of lymphocytes of various subsets were not significantly changed by the ethanol exposure except those showing activation markers which were reduced. The percentage of peripheral blood cells showing markers for macrophage functions and their activation were significantly reduced after binge use of ethanol. Ethanol retarded suppression of cells by retroviral infection. However by 25 weeks of infection there was a 8.6% survival in the ethanol fed mice infected with retrovirus which was much less than virally infected controls. Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice. The second and third morphine injection series suppressed lymphocyte T-helper and T-suppressor cells, but not total T cells. However, suppression by morphine was significantly less during retroviral disease than suppression caused by the virus only. At 25 weeks of infection 44.8% of morphine treated, infected mice survived.

Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment.

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Brun, Paola; Qesari, Marsela; Marconi, Peggy C; Kotsafti, Andromachi; Porzionato, Andrea; Macchi, Veronica; Schwendener, Reto A; Scarpa, Marco; Giron, Maria C; Palù, Giorgio; Calistri, Arianna; Castagliuolo, Ignazio

2018-01-01

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection

Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment

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Paola Brun

2018-03-01

Full Text Available Herpes Simplex Virus type 1 (HSV-1, a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2 to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i liposomes containing dichloromethylene bisphosphonic acid (clodronate to deplete tissue macrophages, (ii CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1

Apoptotic death of Listeria monocytogenes-infected human macrophages induced by lactoferricin B, a bovine lactoferrin-derived peptide.

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Longhi, C; Conte, M P; Ranaldi, S; Penta, M; Valenti, P; Tinari, A; Superti, F; Seganti, L

2005-01-01

Listeria monocytogenes, an intracellular facultative food-borne pathogen, was reported to induce apoptosis in vitro and in vivo in a variety of cell types with the exception of murine macrophages. These cells represent the predominant compartment of bacterial multiplication and die as a result of necrosis. In this study we showed that human non-activated and IFN-gamma-activated macrophagic-like (THP-1) cells infected with L. monocytogenes, mainly die by necrosis rather than by an apoptotic process. Two natural products derived from bovine milk, lactoferrin and its derivative peptide lactoferricin B, are capable of regulating the fate of infected human macrophages. Bovine lactoferrin treatment of macrophages protects them from L. monocytogenes-induced death whereas lactoferricin B, its derivative peptide, determines a shifting of the equilibrium from necrosis to apoptosis.

Downregulation of host tryptophan-aspartate containing coat (TACO gene restricts the entry and survival of Leishmania donovani in human macrophage model

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Venkateswara Reddy Gogulamudi

2015-10-01

Full Text Available Leishmania are obligate intracellular protozoan parasites of mammalian hosts. Promastigotes of Leishmania are internalized by macrophages and transformed into amastigotes in phagosomes, and replicate in phagolysosomes. Phagosomal maturation arrest is known to play a central role in the survival of pathogenic Leishmania within activated macrophages. Recently, tryptophan-aspartate containing coat (TACO gene has been recognized as playing a crucial role in the survival of Mycobacterium tuberculosis within human macrophages by arresting the phagosome maturation process. We postulated that a similar association of TACO gene with phagosomes would prevent the vacuole from maturation in the case of Leishmania. In this study we attempted to define the effect of TACO gene downregulation on the uptake/survival of Leishmania donovani intracellularly, by treatment with Vitamin D3/Retinoic acid (RA & Chenodeoxycholic acid (CDCA/Retinoic acid (RA combinations in human THP-1 macrophages (in vitro. Treatment with these molecules downregulated the TACO gene in macrophages, resulting in reduced parasite load and marked reduction of disease progression in L. donovani infected macrophages. Taken together, these results suggest that TACO gene downregulation may play a role in subverting macrophage machinery in establishing the L.donovani replicative niche inside the host. Our study is the first to highlight the importantrole of the TACO gene in Leishmania entry, and to identify TACO gene downregulation as potential drug target against leishmaniasis.

Alteration of human macrophages microRNA expression profile upon infection with Mycobacterium tuberculosis

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Lucinda Furci

2013-01-01

Conclusions: This study signifies the miRNA host response upon intracellular mycobacterial infection in macrophages, providing new aspects of regulation in host-pathogen interactions, at post-transcriptional levels.

Control of parasitic infections among school children in the peri-urban area of Botucatu, São Paulo, Brazil

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Regina Coeli Cunha Dórea

1996-10-01

Full Text Available Tide prevalence of intestinal parasitosis ivas investigated in a primaiy school located in Rubiâo Júnior, a peri-urban district of Botucatu, São Paulo slate, Brazil, in order to assess the effect of treatment and practical measures of prophylaxis in the control of parasitic infections among 7-to- 18-year-old school children of a low socio-economic status. The first series of parasitological examinations included 219 school children, ef which 123 (56.1 % were found to be infected with one or more parasite species. Eighty- four children canying pathogenic parasites were submitted to various anti-parasitic treatment schedules. We re-evaluated 15 (89 % students after 4 to 6 months post- chemotherapy. The results indicate that the combination of treatment with prophylactic measures has been successful in the control of parasitic infections, since reinfection rates were generally low ( 73-1 % in children infected with most parasite species. The reasons for the apparent failure in the control of infections caused by Hymenolepis nana and Strongyloides stercoralis are discussed.

Parasitic helminths and HIV-1 infection: the effect of immunomodulatory antigens

NARCIS (Netherlands)

Mouser, E.E.I.M.

2016-01-01

In many regions of the world co-infection with parasitic helminths and HIV-1 is common. Both pathogens have major implications for the host immune system, helminths possess immunomodulatory properties whilst HIV-1 infects and kills immune cells. Currently very little is known regarding what effects

The parasitic castration and gigantism of Lymnaea truncatula infected with the larval stages of Fasciola hepatica.

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Wilson, R A; Denison, J

1980-01-01

The shells of Lymnaea truncatula infected with the larval stages of Fasciola hepatica were significantly longer than those of comparable uninfected controls. The dry mass (tissue, shell + parasite) of the same infected snails, 56 days after infection, was approximately twice that of the controls (tissue + shell). The increased mass of infected snails was not due to a disproportionate increase in shell weight relative to tissues. Infected snails maintained at 20 degrees C had virtually ceased egg production by 21 days post-infection whereas control snails continued to lay eggs steadily for the duration of the experiment. The dry mass of snail tissue plus the cumulative dry weight of eggs produced was taken as an indication of the ability of control snails to generate biomass. Similarly the tissue mass plus cumulative egg weight and parasite weight was taken as an indication of the ability of the infected snails to generate biomass. The control and infected snails were not significantly different in this respect indicating that the gigantism of infected snails could be the result of a switch in nutrient supply from reproduction to somatic tissue growth and parasite growth. Castration was brought about 17-21 days after infection as a result of the direct consumption of the ovotestis by a proportion of the redial population. In a separate experiment it was demonstrated that a population of infected snails maintained at 20 degrees C survived as long as a similar group of control snails. The findings with this host-parasite system are discussed in relation to possible mechanisms causing castration and gigantism in other digene-snail interactions, and in relation to parasitic castration in other groups. It is concluded that the observed gigantism of infected snails is more likely to have a nutritional rather than endocrine origin.

Schistosoma mansoni infection suppresses the growth of Plasmodium yoelii parasites in the liver and reduces gametocyte infectivity to mosquitoes.

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Taeko Moriyasu

2018-01-01

Full Text Available Malaria and schistosomiasis are major parasitic diseases causing morbidity and mortality in the tropics. Epidemiological surveys have revealed coinfection rates of up to 30% among children in Sub-Saharan Africa. To investigate the impact of coinfection of these two parasites on disease epidemiology and pathology, we carried out coinfection studies using Plasmodium yoelii and Schistosoma mansoni in mice. Malaria parasite growth in the liver following sporozoite inoculation is significantly inhibited in mice infected with S. mansoni, so that when low numbers of sporozoites are inoculated, there is a large reduction in the percentage of mice that go on to develop blood stage malaria. Furthermore, gametocyte infectivity is much reduced in mice with S. mansoni infections. These results have profound implications for understanding the interactions between Plasmodium and Schistosoma species, and have implications for the control of malaria in schistosome endemic areas.

Parasitic infections of anurans from an urbanized rainforest biotope ...

African Journals Online (AJOL)

The parasitic infections of anurans in an urbanized rainforest biotope in the Diobu, Port Harcourt area of Rivers State were investigated. The few anuran species encountered included Afrixalus fulvovittatus, Amietophrynus regularis, A. cameroonensis, Hyperolius concolor phase B, Hyperolius concolor phase C, ...

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.

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Tajebe, Fitsumbrhan; Getahun, Mulusew; Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew; Kropf, Pascale

2017-07-01

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity.

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites

Science.gov (United States)

Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew

2017-01-01

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity. PMID:28732017

Expression of parasite genetic variation changes over the course of infection: implications of within-host dynamics for the evolution of virulence.

Science.gov (United States)

Clerc, Melanie; Ebert, Dieter; Hall, Matthew D

2015-04-07

How infectious disease agents interact with their host changes during the course of infection and can alter the expression of disease-related traits. Yet by measuring parasite life-history traits at one or few moments during infection, studies have overlooked the impact of variable parasite growth trajectories on disease evolution. Here we show that infection-age-specific estimates of host and parasite fitness components can reveal new insight into the evolution of parasites. We do so by characterizing the within-host dynamics over an entire infection period for five genotypes of the castrating bacterial parasite Pasteuria ramosa infecting the crustacean Daphnia magna. Our results reveal that genetic variation for parasite-induced gigantism, host castration and parasite spore loads increases with the age of infection. Driving these patterns appears to be variation in how well the parasite maintains control of host reproduction late in the infection process. We discuss the evolutionary consequences of this finding with regard to natural selection acting on different ages of infection and the mechanism underlying the maintenance of castration efficiency. Our results highlight how elucidating within-host dynamics can shed light on the selective forces that shape infection strategies and the evolution of virulence. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Alternative states and population crashes in a resource-susceptible-infected model for planktonic parasites and hosts

NARCIS (Netherlands)

Gerla, D.J.; Gsell, A.S.; Kooi, B.W.; Ibelings, B.W.; Donk, van E.; Mooij, W.M.

2013-01-01

1. Despite the strong impact parasites can have, only few models of phytoplankton ecology or aquatic food webs have specifically included parasitism. 2. Here, we provide a susceptible-infected model for a diatom-chytrid hostparasite system that explicitly includes nutrients, infected and uninfected

Wild Anopheles funestus mosquito genotypes are permissive for infection with the rodent malaria parasite, Plasmodium berghei.

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Jiannong Xu

Full Text Available Malaria parasites undergo complex developmental transitions within the mosquito vector. A commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, P. berghei. Anopheles funestus is a major malaria vector in sub-Saharan Africa but has received less attention than the sympatric species, Anopheles gambiae. The imminent completion of the A. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in this mosquito, but previous reports suggested that A. funestus is not permissive for P. berghei development.An A. funestus population was generated in the laboratory by capturing female wild mosquitoes in Mali, allowing them to oviposit, and rearing the eggs to adults. These F1 progeny of wild mosquitoes were allowed to feed on mice infected with a fluorescent P. berghei strain. Fluorescence microscopy was used to track parasite development inside the mosquito, salivary gland sporozoites were tested for infectivity to mice, and parasite development in A. funestus was compared to A. gambiae.P. berghei oocysts were detectable on A. funestus midguts by 7 days post-infection. By 18-20 days post-infection, sporozoites had invaded the median and distal lateral lobes of the salivary glands, and hemocoel sporozoites were observed in the hemolymph. Mosquitoes were capable of infecting mice via bite, demonstrating that A. funestus supports the complete life cycle of P. berghei. In a random sample of wild mosquito genotypes, A. funestus prevalence of infection and the characteristics of parasite development were similar to that observed in A. gambiae-P. berghei infections.The data presented in this study establish an experimental laboratory model for Plasmodium infection of A. funestus, an important vector of human malaria. Studying A. funestus-Plasmodium interactions is now feasible in a laboratory setting. This information lays the groundwork for exploitation of the

Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP

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Temerozo, Jairo R.; Joaquim, Rafael; Regis, Eduardo G.; Savino, Wilson; Bou-Habib, Dumith Chequer

2013-01-01

It is well established that host factors can modulate HIV-1 replication in macrophages, critical cells in the pathogenesis of HIV-1 infection due to their ability to continuously produce virus. The neuropeptides VIP and PACAP induce well-characterized effects on macrophages through binding to the G protein-coupled receptors VPAC1, VPAC2 and PAC1, but their influence on HIV-1 production by these cells has not been established. Here, we describe that VIP and PACAP reduce macrophage production of HIV-1, acting in a synergistic or additive manner to decrease viral growth. Using receptor antagonists, we detected that the HIV-1 inhibition promoted by VIP is dependent on its ligation to VPAC1/2, whereas PACAP decreases HIV-1 growth via activation of the VPAC1/2 and PAC1 receptors. Specific agonists of VPAC2 or PAC1 decrease macrophage production of HIV-1, whereas sole activation of VPAC1 enhances viral growth. However, the combination of specific agonists mimicking the receptor preference of the natural neuropeptides reproduces the ability of VIP and PACAP to increase macrophage resistance to HIV-1 replication. VIP and PACAP up-regulated macrophage secretion of the β-chemokines CCL3 and CCL5 and the cytokine IL-10, whose neutralization reversed the neuropeptide-induced inhibition of HIV-1 replication. Our results suggest that VIP and PACAP and the receptors VPAC2 and PAC1 could be used as targets for developing alternative therapeutic strategies for HIV-1 infection. PMID:23818986

Two's a crowd? Crowding effect in a parasitic castrator drives differences in reproductive resource allocation in single vs double infections.

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Fong, Caitlin R; Moron, Nancy A; Kuris, Armand M

2017-04-01

The 'crowding effect' is a result of competition by parasites within a host for finite resources. Typically, the severity of this effect increases with increasing numbers of parasites within a host and manifests in reduced body size and thus fitness. Evidence for the crowding effect is mixed - while some have found negative effects, others have found a positive effect of increased parasite load on parasite fitness. Parasites are consumers with diverse trophic strategies reflected in their life history traits. These distinctions are useful to predict the effects of crowding. We studied a parasitic castrator, a parasite that usurps host reproductive energy and renders the host sterile. Parasitic castrators typically occur as single infections within hosts. With multiple parasitic castrators, we expect strong competition and evidence of crowding. We directly assess the effect of crowding on reproductive success in a barnacle population infected by a unique parasitic castrator, Hemioniscus balani, an isopod parasite that infects and blocks reproduction of barnacles. We find (1) strong evidence of crowding in double infections, (2) increased frequency of double infections in larger barnacle hosts with more resources and (3) perfect compensation in egg production, supporting strong space limitation. Our results document that the effects of crowding are particularly severe for this parasitic castrator, and may be applicable to other castrators that are also resource or space limited.

Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages.

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Antje Bast

2014-03-01

Full Text Available The cytosolic pathogen Burkholderia pseudomallei and causative agent of melioidosis has been shown to regulate IL-1β and IL-18 production through NOD-like receptor NLRP3 and pyroptosis via NLRC4. Downstream signalling pathways of those receptors and other cell death mechanisms induced during B. pseudomallei infection have not been addressed so far in detail. Furthermore, the role of B. pseudomallei factors in inflammasome activation is still ill defined. In the present study we show that caspase-1 processing and pyroptosis is exclusively dependent on NLRC4, but not on NLRP3 in the early phase of macrophage infection, whereas at later time points caspase-1 activation and cell death is NLRC4- independent. In the early phase we identified an activation pathway involving caspases-9, -7 and PARP downstream of NLRC4 and caspase-1. Analyses of caspase-1/11-deficient infected macrophages revealed a strong induction of apoptosis, which is dependent on activation of apoptotic initiator and effector caspases. The early activation pathway of caspase-1 in macrophages was markedly reduced or completely abolished after infection with a B. pseudomallei flagellin FliC or a T3SS3 BsaU mutant. Studies using cells transfected with the wild-type and mutated T3SS3 effector protein BopE indicated also a role of this protein in caspase-1 processing. A T3SS3 inner rod protein BsaK mutant failed to activate caspase-1, revealed higher intracellular counts, reduced cell death and IL-1β secretion during early but not during late macrophage infection compared to the wild-type. Intranasal infection of BALB/c mice with the BsaK mutant displayed a strongly decreased mortality, lower bacterial loads in organs, and reduced levels of IL-1β, myeloperoxidase and neutrophils in bronchoalveolar lavage fluid. In conclusion, our results indicate a major role for a functional T3SS3 in early NLRC4-mediated caspase-1 activation and pyroptosis and a contribution of late caspase-1

Protein energy malnutrition increases arginase activity in monocytes and macrophages.

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Corware, Karina; Yardley, Vanessa; Mack, Christopher; Schuster, Steffen; Al-Hassi, Hafid; Herath, Shanthi; Bergin, Philip; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Kropf, Pascale

2014-01-01

Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

Intestinal parasitic infections and malnutrition amongst first-cycle primary schoolchildren in Adama, Ethiopia

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Getachew Belay

2011-05-01

Objectives: The objective of this study was to investigate the magnitude of intestinal parasitic infections and malnutrition amongst first-cycle primary schoolchildren in Adama town,Ethiopia. Method: A total of 358 children from four primary schools in Adama town were included for stool examination, weight for age, height for age, weight for height and socio-economic status of the family. Results: The result of stool examinations showed that 127 (35.5% of the study subjects were infected by one or more parasite. The most frequent parasites were Entamoeba histolytica/dispar (12.6% and Hymenolopis nana (8.9%. The rate of intestinal parasitic infection was not significantly associated with sex, age or socio-economic factors and nutrition (P > 0.05. The overall prevalence of malnutrition was 21.2%. Those children whose families had a monthly income of less than 200 ETB (Ethiopian birr were highly affected by malnutrition (P < 0.05,but family education was not identified as a factor for malnutrition amongst schoolchildren. Conclusion: The prevalence of E. histolytica/dispar and H. nana could be of public health importance and calls for appropriate control strategies, and the high prevalence of malnutrition amongst children from poor families requires intervention.

Multi-Level Determinants of Parasitic Fly Infection in Forest Passerines

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Manzoli, Darío Ezequiel; Antoniazzi, Leandro Raúl; Saravia, María José; Silvestri, Leonardo; Rorhmann, David; Beldomenico, Pablo Martín

2013-01-01

The study of myiasis is important because they may cause problems to the livestock industry, public health, or wildlife conservation. The ecology of parasitic dipterans that cause myiasis is singular, as they actively seek their hosts over relatively long distances. However, studies that address the determinants of myiasis dynamics are very scarce. The genus Philornis include species that may be excellent models to study myiasis ecology, as they exclusively parasitize bird nestlings, which stay in their nests until they are fully fledged, and larvae remain at the point of entry until the parasitic stage is over, thus allowing the collection of sequential individual-level infection data from virtually all the hosts present at a particular area. Here we offer a stratified multi-level analysis of longitudinal data of Philornis torquans parasitism in replicated forest bird communities of central Argentina. Using Generalized Linear Models and Generalized Linear Mixed Models and an information theory approach for model selection, we conducted four groups of analyses, each with a different study unit, the individual, the brood, the community at a given week, and the community at a given year. The response variable was larval abundance per nestling or mean abundance per nestling. At each level, models included the variables of interest of that particular level, and also potential confounders and effect modifiers of higher levels. We found associations of large magnitude at all levels, but only few variables truly governed the dynamics of this parasite. At the individual level, the infection was determined by the species and the age of the host. The main driver of parasite abundance at the microhabitat level was the average height of the forest, and at the community level, the density of hosts and prior rainfall. This multi-level approach contributed to a better understanding of the ecology of myiasis. PMID:23874408

Tracking transparent monogenean parasites on fish from infection to maturity

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Alejandro Trujillo-González

2015-12-01

Full Text Available The infection dynamics and distribution of the ectoparasitic fish monogenean Neobenedenia sp. (Monogenea: Capsalidae throughout its development was examined on barramundi, Lates calcarifer (Bloch (Latidae, by labelling transparent, ciliated larvae (oncomiracidia with a fluorescent dye. Replicate fish were each exposed to approximately 50 fluorescent oncomiracidia and then examined for parasites using an epifluorescence stereomicroscope at 10 time intervals post-exposure (15, 30, 60, 120 min, 24, 48 h, four, eight, 12, and 16 days. Fluorescent labelling revealed that parasites attached underneath and on the surface of the scales of host fish. Parasite infection success was 20% within 15 min, and peaked at 93% two days post-exposure, before gradually declining between four and sixteen days. Differences in parasite distribution on L. calcarifer over time provided strong evidence that Neobenedenia sp. larvae settled opportunistically and then migrated to specific microhabitats. Parasites initially attached (<24 h in greater mean numbers on the body surface (13 ± 1.5 compared to the fins (4 ± 0.42 and head region (2 ± 0.41. Once larvae recruitment had ceased (48 h, there were significantly higher mean post-larvae counts on the head (5 ± 3.4 and fins (12 ± 3 compared to previous time intervals. Neobenedenia sp. aggregated on the eyes, fins, and dorsal and ventral extremities on the main body. As parasites neared sexual maturity, there was a marked aggregation on the fins (22 ± 2.35 compared to the head (4 ± 0.97 and body (9 ± 1.33, indicating that Neobenedenia sp. may form mating aggregations.

UNC93B1 mediates host resistance to infection with Toxoplasma gondii.

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Mariane B Melo

2010-08-01

Full Text Available UNC93B1 associates with Toll-Like Receptor (TLR 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of Toxoplasma replication by macrophages.

Intestinal parasite infection in children from primary school in Florianopolis (SC – environmental and health education

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José Roberto S. A. Leite

2008-12-01

Full Text Available Parasite infection remains an important public health problem in many areas around the world as well as in Brazil, and it is frequently associated with poverty and lack of sanitation facilities. A coprological investigation was conducted in children from the primary school Intendente Aricomedes da Silva in Florianopolis, Brazil, in order to determine the prevalence of intestinal parasite infections. Also a series of indoor and outdoor activities were carried out to improve the awareness of students, parents, and school staff about parasite infection. Fecal samples from 101 school children and 5 school adult staff were collected and analyzed from June to December 2006. Thirty-eight individuals (35.8% were positive for at least one parasite. Ascaris lumbricoides, the most frequent helminth, was prevalent in 5.7% of individuals. Entamoeba coli and Endolimax nana were the most prevalent protozoa in this study: 20.7% and 12.3% respectively. Although non pathogenic protozoa species, they indicate oral-fecal contamination. Infected individuals were sent to the Health Unit for treatment. Finally, a meeting with the school community was organized to discuss how to prevent intestinal parasite infections by improving basic hygiene habits and best practice with water, food and environment.

An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

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Bowden, Steven D; Ramachandran, Vinoy K; Knudsen, Gitte M; Hinton, Jay C D; Thompson, Arthur

2010-11-08

In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice. We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence. Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous.

The magnitude and risk factors of intestinal parasitic infection in relation to Human Immunodeficiency Virus infection and immune status, at ALERT Hospital, Addis Ababa, Ethiopia.

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Taye, Biruhalem; Desta, Kassu; Ejigu, Selamawit; Dori, Geme Urge

2014-06-01

Human Immunodeficiency Virus (HIV) and intestinal parasitic infections are among the main health problems in developing countries like Ethiopia. Particularly, co-infections of these diseases would worsen the progression of HIV to Acquired Immunodeficiency Syndrome (AIDS). The purpose of this study was to determine the magnitude and risk factors for intestinal parasites in relation to HIV infection and immune status. The study was conducted in (1) HIV positive on antiretroviral therapy (ART) and (2) ART naïve HIV positive patients, and (3) HIV-negative individuals, at All African Leprosy and Tuberculosis (TB) Eradication and Rehabilitation Training Center (ALERT) hospital in Addis Ababa, Ethiopia. Study participants were interviewed using structured questionnaires to obtain socio-demographic characteristics and assess risk factors associated with intestinal parasitic infection. Intestinal parasites were identified from fecal samples by direct wet mount, formol ether concentration, and modified Ziehl-Neelsen staining techniques. The immune status was assessed by measuring whole blood CD4 T-cell count. The overall magnitude of intestinal parasite was 35.08%. This proportion was different among study groups with 39.2% (69/176), 38.83% (40/103) and 27.14% (38/140) in ART naïve HIV positives patients, in HIV negatives, and in HIV positive on ART patients respectively. HIV positive patients on ART had significantly lower magnitude of intestinal parasitic infection compared to HIV negative individuals. Intestinal helminths were significantly lower in HIV positive on ART and ART naïve patients than HIV negatives. Low monthly income, and being married, divorced or widowed were among the socio-demographic characteristics associated with intestinal parasitic infection. No association was observed between the magnitude of intestinal parasites and CD4 T-cell count. However, Cryptosporidium parvum, and Isospora belli were exclusively identified in individuals with CD4 T

Higher expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 chemokines in the skin associated with parasite density in canine visceral leishmaniasis.

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Daniel Menezes-Souza

Full Text Available BACKGROUND: The immune response in the skin of dogs infected with Leishmania infantum is poorly understood, and limited studies have described the immunopathological profile with regard to distinct levels of tissue parasitism and the clinical progression of canine visceral leishmaniasis (CVL. METHODOLOGY/PRINCIPAL FINDINGS: A detailed analysis of inflammatory cells (neutrophils, eosinophils, mast cells, lymphocytes, and macrophages as well as the expression of chemokines (CCL2, CCL4, CCL5, CCL13, CCL17, CCL21, CCL24, and CXCL8 was carried out in dermis skin samples from 35 dogs that were naturally infected with L. infantum. The analysis was based on real-time polymerase chain reaction (PCR in the context of skin parasitism and the clinical status of CVL. We demonstrated increased inflammatory infiltrate composed mainly of mononuclear cells in the skin of animals with severe forms of CVL and high parasite density. Analysis of the inflammatory cell profile of the skin revealed an increase in the number of macrophages and reductions in lymphocytes, eosinophils, and mast cells that correlated with clinical progression of the disease. Additionally, enhanced parasite density was correlated with an increase in macrophages and decreases in eosinophils and mast cells. The chemokine mRNA expression demonstrated that enhanced parasite density was positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. CONCLUSIONS/SIGNIFICANCE: These findings represent an advance in the knowledge about skin inflammatory infiltrates in CVL and the systemic consequences. Additionally, the findings may contribute to the design of new and more efficient prophylactic tools and immunological therapies against CVL.

Gastrointestinal parasitic infection in diverse species of domestic ruminants inhabiting tribal rural areas of southern Rajasthan, India.

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Choubisa, S L; Jaroli, V J

2013-10-01

A total of 415 adult domesticated ruminants, 130 cattle (Bos taurus), 108 buffaloes (Bubalus bubalis), 94 goats (Capra hircus) and 83 sheep (Ovis aries) inhabiting tribal rural areas of southern Rajasthan, India were investigated for evidence of gastrointestinal protozoan and helminthic infections. In southern Rajasthan humid ecosystem is predominant and has number of perennial freshwater bodies. Fresh faecal samples of these animals were examined microscopically by direct wet smear with saline and 1 % Lugol's iodine and formalin ether concentration. Of these 296 (71.32 %) were found to be infected with different species of gastrointestinal parasites. The highest (93.84 %) prevalence of these parasitic infections was found in cattle followed by goats (82.97 %), sheep (55.42 %) and buffaloes (46.29 %). Except cattle no other ruminants revealed protozoan infection. A total 8 species of gastrointestinal parasites were encountered. Among these parasites Fasciola hepatica was the commonest (15.18 %) followed by Haemonchus contortus (11.32 %), Ancylostoma duodenale (10.36 %), Trichuris trichiura (9.15 %), Amphistome species (7.95 %), Moniezia expansa (6.98 %), Strongyloides stercoralis (4.57 %) and Balantidium coli (3.37 %). The prevalence rate of these parasitic infections also varied seasonally. The highest prevalence rate was found in rainy season (84.21 %) followed by winter (73.9 %) and summer (52.8 %). The possible causes for variation in prevalence of parasitic infections are also discussed.

Geophagy and parasitic infections in pregnant women attending an ...

African Journals Online (AJOL)

Background: Geophagy, a regular and deliberate habit of eating non-food substances is practiced worldwide and in sub-Saharan Africa. ... was not associated with parasitic infections in pregnant women, geophagy was found to have a significant association with education, history of geophagy and the feeding problems.

Effect of Macrophage Migration Inhibitory Factor (MIF) in Human Placental Explants Infected with Toxoplasma gondii Depends on Gestational Age

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de Oliveira Gomes, Angelica; de Oliveira Silva, Deise Aparecida; Silva, Neide Maria; de Freitas Barbosa, Bellisa; Franco, Priscila Silva; Angeloni, Mariana Bodini; Fermino, Marise Lopes; Roque-Barreira, Maria Cristina; Bechi, Nicoletta; Paulesu, Luana Ricci; dos Santos, Maria Célia; Mineo, José Roberto; Ferro, Eloisa Amália Vieira

2011-01-01

Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-β1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age. PMID:21641401

Short-term parasite-infection alters already the biomass, activity and functional diversity of soil microbial communities

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Li, Jun-Min; Jin, Ze-Xin; Hagedorn, Frank; Li, Mai-He

2014-11-01

Native parasitic plants may be used to infect and control invasive plants. We established microcosms with invasive Mikania micrantha and native Coix lacryma-jobi growing in mixture on native soils, with M. micrantha being infected by parasitic Cuscuta campestris at four intensity levels for seven weeks to estimate the top-down effects of plant parasitism on the biomass and functional diversity of soil microbial communities. Parasitism significantly decreased root biomass and altered soil microbial communities. Soil microbial biomass decreased, but soil respiration increased at the two higher infection levels, indicating a strong stimulation of soil microbial metabolic activity (+180%). Moreover, a Biolog assay showed that the infection resulted in a significant change in the functional diversity indices of soil microbial communities. Pearson correlation analysis indicated that microbial biomass declined significantly with decreasing root biomass, particularly of the invasive M. micrantha. Also, the functional diversity indices of soil microbial communities were positively correlated with soil microbial biomass. Therefore, the negative effects on the biomass, activity and functional diversity of soil microbial community by the seven week long plant parasitism was very likely caused by decreased root biomass and root exudation of the invasive M. micrantha.

Parasitic Infections (Helminth and Protozoa in Cases Referring to Yazd Central Laboratory, 2002-2004

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AA Dehghani

2008-01-01

Full Text Available Introduction: Intestinal parasites have world wide prevalence and are considered to be as one of the leading hygienic and economic problems in the world. It can be said that there is nowhere in the world without parasitic infestations. The present study was conducted to determine the prevalence of intestinal parasites in patients referring to Yazd Central Laboratory in 2000-2002. Methods: The present study was a cross-sectional, analytic and descriptive study including 13388 stool specimens examined by two methods; Formalin-Ethyl Acetate and direct Method for intestinal parasites and Scotch tape method for Enterobius vermicularis. Results: 13388 samples examined included 6913 women and 6475 men. Parasites were observed in 1151 cases (8.6% including 618 (53.7% men and 533 (46.3% women, respectively. Of these, 98.6% were infected with protozoa and 1.4% with helminths. Giardia lambdia (41.05%, E.coli (27.45% and Blastocystis hominis (15.51% were the most common infecting organisms. Helminth infections were few, but the highest frequency was related to Hymenolepis nana and Enterobious vermicularis. Maximum frequency was reported in summer. There was a significant association between stool consistency and infestation by intestinal parasites (P=0.002. There was a significant relationship with sex, too (P=0.001 Conclusion: In the present study, the most common parasites were Giardia, E.coli and Blastocystis hominis (higher than five, but the prevalence was less as compared to previous similar studies in other regions, which could be because of the hot and dry weather, better personal hygiene and improved sewage system of Yazd.

Zoonotic enteric parasites transmitted from dogs in Egypt with special concern to Toxocara canis infection

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Awadallah, Maysa A. I.; Salem, Lobna M. A.

2015-01-01

Aim: This work aimed to study the role played by dogs in transmitting zoonotic enteric parasites to humans in Egypt and to analyze the risk factors associated with the occurrence of such infection in dogs. Serodiagnosis of anti-Toxocara immunoglobulin G (IgG) antibodies among human beings as well as analyzing risk factors predispose to Toxocara canis infection in human beings are another objectives of this study. Materials and Methods: From June to December 2013, a total of 130 fecal samples from 4 dog populations (Military, nomadic and domiciled dogs from rural and high standard districts) and 150 stool samples of 6 occupational groups were examined for the presence of enteric parasitic infection. Moreover, 150 serum samples were collected from humans from whom stool samples were collected and examined for the presence of anti-T. canis antibodies. Results: Enteric parasites were detected in 30% of fecal samples from 4 dog populations in Egypt. High infectivity had been reported in nomadic dogs (63.33%) (Crude odds ratios [COR]=67.36, 95% confidence interval [CI]=8.09-560.8, p0.05) did not seem to have a significant association among the examined dogs. Enteric parasitic infection was reported in 31/150 human stools (20.67%). Students were the most affected groups (37.14%), followed by nomadic people (24%), house wives (20%), house guarders and military workers (12%, each), and employees (10%). The identified parasites were Cryptosporidium spp. (9.33%), Ascaris lumbercoides (3.33%), Heterophyes spp. and Ancylostoma spp. (2.66%, each) and Paragonimus spp. and Hymenolepis nana (1.33%, each). Toxocara IgG antibodies were detected in 36/150 (24%) serum samples investigated. Toxocara IgG antibodies were more prevalent in males (26.66%) than females (20%). Seroprevalence was highest (17/35, 48.57%) in 7-15 years old (COR=6.93, 95% CI=1.75-27.43, p=0.006). Seroprevalence values for T. canis antibodies were higher in those; raising dogs (29.85%), eating raw vegetables (25

Parasitic anemone infects the invasive ctenophore Mnemiopsis leidyi in the North East Atlantic

DEFF Research Database (Denmark)

Selander, Erik; Møller, Lene Friis; Sundberg, Per

2010-01-01

We report of the first finding of parasitic sea anemone larvae infecting the invasive ctenophore Mnemiopsis leidyi in the North East Atlantic. Parasitic anemone larvae are common in the native habitat of Mnemiopsis, but have not previously been reported from any of the locations where Mnemiopsis ...

Intestinal parasitic infections and the level of immunosuppression in ...

African Journals Online (AJOL)

Background: Opportunistic and non-opportunistic intestinal parasites play a significant role in the morbidity and mortality of HIV/AIDS-infected patients. The frequency of their occurrence strongly correlates with the patient's level of immunity. The most ..... Conflict of interest: Authors declare that they have no conflict of interest.

The Impact of Intestinal Parasitic Infections on the Nutritional Status of Rural and Urban School-Aged Children in Nigeria.

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Opara, Kenneth N; Udoidung, Nsima I; Opara, Dominic C; Okon, Okpok E; Edosomwan, Evelyn U; Udoh, Anietie J

2012-01-01

Intestinal parasitic infection and undernutrition are still major public health problems in poor and developing countries. The objective of this study was to assess the relationship between intestinal parasitic infection and nutritional status in 405 primary school children from rural and urban areas of Akwa Ibom State, Nigeria. This cross-sectional survey in 2009 obtained anthropometric data, height-for-age (HA), weight-for-height (WH) and weight-for-age (WA) Z-scores from each child and fecal samples were also collected and screened for intestinal parasites using standard parasitological protocols. The prevalence of infection with any intestinal parasite was 67.4%. A total of six intestinal parasites were detected; hookworm (41.7%) had the highest prevalence. The prevalence of intestinal parasites and undernutrition was significantly higher in rural than in urban children (Prural and urban children were 42.3% vs. 29.7%; underweight 43.2% vs. 29.6% and wasting 10.9% vs. 6.4%, respectively. With respect to nutritional indicators, the infected children had significantly (Pmalnutrition, controlling these parasites could increase the physical development and well-being of the affected children.

Infection by Intestinal Parasites, Stunting and Anemia in School-Aged Children from Southern Angola.

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Oliveira, Dinamene; Ferreira, Filipa Santana; Atouguia, Jorge; Fortes, Filomeno; Guerra, António; Centeno-Lima, Sónia

2015-01-01

Intestinal parasites are responsible for morbidity in children worldwide, especially in low income countries. In the present study we determine the prevalence of intestinal parasites and explore its association with anemia and stunting in school-aged children. A cross-sectional study was conducted from September to October 2010 enrolling 328 children attending the primary school in Lubango, the second largest city after the capital Luanda. Stool samples were collected for parasite detection through microscopy and molecular identification of Entamoeba histolytica and Entamoeba dispar. Stunting was assessed using the z-scores of height for age and hemoglobin concentration was determined using a portable hemoglobin analyzing system. The global prevalence of pathogenic intestinal parasites was 44.2%, the most common being Ascaris lumbricoides (22.0%), Giardia lamblia (20.1%) and Hymenolepis nana (8.8%). Molecular detection revealed that 13.1% of the children carried E. dispar and 0.3% were infected with E. histolytica. The prevalence of stunting (mild to severe) was 41.5%. Stunting was more frequent in older children (p = 0.006, OR = 1.886), while anemia was more frequent in younger children (p = 0.005, OR = 2.210). The prevalence of anemia was 21.6%, and we found a significant association with infection by H. nana (p = 0.031, OR = 2.449). This is one of the few published studies reporting intestinal parasites infection, nutritional status and anemia in children from Angola. Furthermore, the present work highlights the importance of regular intestinal parasites screening in children.

Epidemiology of Intestinal Parasite Infections among Kindergarten Children in Mekelle Town, Northern Ethiopia

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Megbaru Alemu; Habtamu Bedemo; Gessessew Bugssa; Sena Bayissa; Kiros Tedla

2015-01-01

Back ground: Intestinal parasitic infections are among the major public health problems in the Sub-Saharan Africa. However, surveys for intestinal parasites conducted in different areas of Ethiopia focused on school age children. Consequently, there is scarcity of data on the burden of intestinal parasites among children in Kindergartens. Material and Method: This cross-sectional study was conducted in three Kindergartens in Mekelle City, North Ethiopia from October to November 2013. A total ...

Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

International Nuclear Information System (INIS)

Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2013-01-01

Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

Parasitic infections on the shore of Lake Victoria (East Africa) detected by Mini-FLOTAC and standard techniques.

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Barda, Beatrice; Ianniello, Davide; Zepheryne, Henry; Rinaldi, Laura; Cringoli, Giuseppe; Burioni, Roberto; Albonico, Marco

2014-09-01

Helminths and protozoa infections pose a great burden especially in developing countries, due to morbidity caused by both acute and chronic infection. The aim of our survey was to analyze the intestinal parasitic burden in communities from Mwanza region, Tanzania. Subjects (n=251) from four villages on the South of Lake Victoria have been analyzed for intestinal parasites with direct smear (DS), formol-ether concentration method (FECM) and the newly developed Mini-FLOTAC technique; urinary schistosomiasis was also assessed in a subsample (n=151); symptoms were registered and correlation between clinic and infections was calculated by chi-squared test and logistical regression. Out of the subjects screened for intestinal and for urinary parasites, 87% (218/251) were found positive for any infection, 69% (174/251) carried a helminthic and 67% (167/251) a protozoan infection, almost half of them had a double or triple infection. The most common helminths were hookworms, followed by Schistosoma mansoni and Schistosoma haematobium. Among protozoa, the most common was Entamoeba coli followed by Entamoeba histolytica/dispar and Giardia intestinalis. Mini-FLOTAC detected a number of helminth infections (61.7%) higher than FECM (38.6%) and DS (17.9%). Some positive associations with abdominal symptoms were found and previous treatment was negatively correlated with infection. Despite the limited size of the examined population the current study indicates a high prevalence of intestinal parasitic infection in Bukumbi area, Tanzania, and Mini-FLOTAC showed to be a promising diagnostic tool for helminth infections. This high parasitic burden calls for starting a regular deworming programme and other preventive interventions in schools and in the community. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential MicroRNA Expression in Human Macrophages with Mycobacterium tuberculosis Infection of Beijing/W and Non-Beijing/W Strain Types.

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Zheng, Lin; Leung, Eric; Lee, Nelson; Lui, Grace; To, Ka-Fai; Chan, Raphael C Y; Ip, Margaret

2015-01-01

The role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls. The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (PmicroRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems. We showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections.

Prevalence and risk factors of intestinal parasitic infections among hill tribe schoolchildren, Northern Thailand

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Tawatchai Apidechkul

2015-09-01

Full Text Available Objective: To study the prevalence and risk factors of intestinal parasitic infections among hill tribe schoolchildren who attended 10 border patrol police schools in 2012, Chiang Rai, Thailand. Methods: A total of 339 subjects were recruited into the study from 2 194 children. Questionnaire was tested for validity and reliability before use. About 5 g stool specimens were collected and investigated for intestinal parasite infections by using cellophane-covered thick smear technique. Logistic regression at α = 0.05 was used to test the associations between variables to find risk factors. Results: There were 339 subjects of whom 51.9% were males and 66.1% were Buddhist; racially 31.2% were Akha and 30.4% were Kmong; mean age was 10.3 years old (minimum = 6, maximum = 16. The prevalence of parasitic infection was 9.7%. After controlling for age, sex, religion, parents’ education levels and parents’ occupations, the only factor that showed a statistically significant association with intestinal parasitic infection was the source of drinking water. The group of drinking mountain piped water had a greater risk of 8.22 times (adjusted odds ratio = 8.22, 95%; confidence interval: 1.07–63.18 compared to the drinking commercially bottled water group, while the group of drinking underground water had a greater risk of 9.83 times (adjusted odds ratio = 9.83, 95%; confidence interval: 0.93–104.12 compared to the drinking commercially bottled water group. Conclusions: Drinking water contaminated by soil was shown to be an important risk factor for intestinal parasitic infection in hill tribe schoolchildren living in mountainous border areas in the northern part of Thailand. Safer alternative drinking water source should be provided along with health education for schools and villagers to be aware of the risk of intestinal parasites from drinking water sources such as mountain piped or underground wells. Such sources are likely to contain higher soil

Prevalence of Intestinal Parasite Infections among Children in the Day Care Centers of Gonbad-e Kavus County, North-Eastern Iran

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Fatemeh Mesgarian

2017-10-01

Full Text Available Background: Intestinal parasite infection is one of the major health problems in the world especially in the developing countries. Objectives: This study was an attempt to examine the prevalence of intestinal parasite infection in the day care centers in Gonbad-e Kavus. Methods: In this cross sectional study, 932 children were recruited from 45 day care centers in Gonbad-e Kavus in Iran, through a survey and their stool samples were examined using direct wet mount, formalin-ether concentration and Trichrome staining techniques. Also, scotch tape slides were microscopically analyzed. Data were analyzed using percentage, frequency and Chi-square test using SPSS ver.16. Odds Ratio was used show the effect size of socio-demographic variables on the rate of intestinal parasite infection. Results: The prevalence of intestinal parasite infections among the children was 26.6%. This study found a significant relationship between the children age, parent education and the place of residency with the rate of intestinal parasite infection (P < 0.05. The children in rural areas were 1.55 times more likely than the children in urban areas to be infected with intestinal parasites (OR = 1.55. Moreover, the results of this study showed that an increase in parent’s education for one level decreased the risk of infection in their children by 6% (OR = 0.94. Also, with a rise in the age of participants for a year, the risk of infection increased by 44% (OR = 1.44. Conclusions: Due to the high rate of intestinal parasite infections among children, parents and child care workers need to learn about the various means by which parasites can be transmitted in day care centers.

Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.

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Xiaojun Chen

2014-05-01

Full Text Available Following Schistosoma japonicum (S. japonicum infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

Prevalence of intestinal parasitic infections and associated risk factors among students at Dona Berber primary school, Bahir Dar, Ethiopia.

Science.gov (United States)

Hailegebriel, Tamirat

2017-05-23

Intestinal parasitic infections are still one of the major health concerns in developing countries. Monitoring of intestinal parasitic infection and associated risk factors are essential for intervention strategies. Therefore, the aim of this study was to assess the prevalence of intestinal parasitic infection and associated risk factors among students at Dona Berber primary school, Bahir Dar, Ethiopia. School based cross-sectional study was conducted among students at Dona Berber primary school from October 2015 to June 2016. Three hundred fifty nine students were involved in the study by providing stool specimens and detailed personal information. Students were selected by stratified and systematic random sampling method. Fresh stool samples were collected from each student and processed by formal-ether fecal concentration technique. Data were analyzed using SPSS version 20.0 statistical software and p value intestinal parasites. The rates of single and double parasitic infections among students were 49.6% and 16.2%, respectively. The most prevalent parasite detected in the study was E. histolytica/dispar (24.5%) followed by hookworm (22.8%). Among the different variables assessed in the study, family size of 6 (AOR = 4.90; 95% CI, 2.03-11.83), irregularly shoe wearing habit (AOR = 2.85; 95% CI, 1.53-5.32) and unclean finger nail (AOR = 3.68; 95% CI, 1.87-7.26) were independently predict intestinal parasitic infections. Student drinking well water (AOR = 2.51; 95% CI, 2.30-4.86) and unclean finger nail (AOR = 4.42; 95% CI, 2.55-7.65) were strongly associated with E. histolytica/dispar infection. Likewise, irregular shoe wearing habit (AOR = 14.13; 95% CI, 7.06-28.29) was strongly associated with hookworm infections. High prevalence of intestinal parasitic infection among the study participants demands improvement of health education, environmental sanitation and quality of water sources.

Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.

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Nandi, Ajeya; Bishayi, Biswadev

2016-02-01

C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.

Trickle or clumped infection process? A stochastic model for the infection process of the parasitic roundworm of humans, Ascaris lumbricoides.

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Walker, Martin; Hall, Andrew; Basáñez, María-Gloria

2010-10-01

The importance of the mode of acquisition of infectious stages of directly-transmitted parasitic helminths has been acknowledged in population dynamics models; hosts may acquire eggs/larvae singly in a "trickle" type manner or in "clumps". Such models have shown that the mode of acquisition influences the distribution and dynamics of parasite loads, the stability of host-parasite systems and the rate of emergence of anthelmintic resistance, yet very few field studies have allowed these questions to be explored with empirical data. We have analysed individual worm weight data for the parasitic roundworm of humans, Ascaris lumbricoides, collected from a three-round chemo-expulsion study in Dhaka, Bangladesh, with the aim of discerning whether a trickle or a clumped infection process predominates. We found that hosts tend to harbour female worms of a similar weight, indicative of a clumped infection process, but acknowledged that unmeasured host heterogeneities (random effects) could not be completely excluded as a cause. Here, we complement our previous statistical analyses using a stochastic infection model to simulate sizes of individual A. lumbricoides infecting a population of humans. We use the intraclass correlation coefficient (ICC) as a quantitative measure of similarity among simulated worm sizes and explore the behaviour of this statistic under assumptions corresponding to trickle or clumped infections and unmeasured host heterogeneities. We confirm that both mechanisms are capable of generating aggregates of similar-sized worms, but that the particular pattern of ICCs described pre- and post-anthelmintic treatment in the data is more consistent with aggregation generated by clumped infections than by host heterogeneities alone. This provides support to the notion that worms may be acquired in clumps. We discuss our results in terms of the population biology of A. lumbricoides and highlight the significance of our modelling approach for the study of the

Zoonotic enteric parasites transmitted from dogs in Egypt with special concern to Toxocara canis infection

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Maysa A. I. Awadallah

2015-08-01

Full Text Available Aim: This work aimed to study the role played by dogs in transmitting zoonotic enteric parasites to humans in Egypt and to analyze the risk factors associated with the occurrence of such infection in dogs. Serodiagnosis of anti-Toxocara immunoglobulin G (IgG antibodies among human beings as well as analyzing risk factors predispose to Toxocara canis infection in human beings are another objectives of this study. Materials and Methods: From June to December 2013, a total of 130 fecal samples from 4 dog populations (Military, nomadic and domiciled dogs from rural and high standard districts and 150 stool samples of 6 occupational groups were examined for the presence of enteric parasitic infection. Moreover, 150 serum samples were collected from humans from whom stool samples were collected and examined for the presence of anti-T. canis antibodies. Results: Enteric parasites were detected in 30% of fecal samples from 4 dog populations in Egypt. High infectivity had been reported in nomadic dogs (63.33% (Crude odds ratios [COR]=67.36, 95% confidence interval [CI]=8.09-560.8, p˂0.000, followed by domiciled dogs from rural areas (40% (COR=26, 95% CI=3.14-215.54, p=0.003, domiciled dogs from high standard areas (23.33% (COR=11.87, 95% CI=1.37-102.69, p=0.025 and military dogs (2.5%. Twelve species of enteric parasites were identified, Ancylostomatidae (6.15%, T. canis and Cryptosporidium spp. (5.38%, each, Heterophyes spp. (3.85%, Toxocara leonina and Blastocystis spp. (3.07%, Taenidae eggs (2.31%, Hymenolepis diminuta (1.54% and Entamoeba canis, Cyclospora cayetanensis, and Paragonimus spp. (0.77%, each. Univariate logestic regression revealed significant association of age (COR=4.73, 95% CI=2.13-10.53, p˂0.000, gender (COR=2.63, 95% CI=1.22-5.68, p˂0.014, housing system (COR=5.10, 95% CI=2.04-12.75, p˂0.000 with enteric parasitic infection in dogs. However, breeds (COR=6.91, 95% CI=0.88-54.52, p=0.067 and type of feeding (COR ranged from 3.5 to

Survey of gastrointestinal parasite infection in African lion ( Panthera ...

African Journals Online (AJOL)

Little is known about gastrointestinal parasite infections in large carnivores in Africa and what is available is largely from East Africa. We collected faecal samples from nine spotted hyaenas (Crocuta crocuta), 15 lions (Panthera leo) and 13 African wild dog (Lycaon pictus) from Luangwa Valley, Zambia. The most common ...

Maintaining the immunological balance in parasitic infections: a role for TGF-ß?

DEFF Research Database (Denmark)

Omer, F M; Kurtzhals, J A; Riley, E M

2000-01-01

on the one hand and prevention of immune-mediated pathology on the other. In this article, Fakhereldin Omer, Jørgen Kurtzhals and Eleanor Riley review the immunoregulatory properties of TGF-beta in the context of parasitic infections. Data from murine malaria infections suggest that TGF-beta modifies...

Leishmania major methionine sulfoxide reductase A is required for resistance to oxidative stress and efficient replication in macrophages.

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Fiona M Sansom

Full Text Available Leishmania are protozoan parasites that proliferate within the phagolysome of mammalian macrophages. While a number of anti-oxidant systems in these parasites have been shown to protect against endogenous as well as host-generated reactive oxygen species, the potential role of enzymes involved in the repair of oxidatively damaged proteins remains uncharacterized. The Leishmania spp genomes encode a single putative methionine sulfoxide reductase (MsrA that could have a role in reducing oxidized free and proteinogenic methionine residues. A GFP-fusion of L. major MsrA was shown to have a cytoplasmic localization by immunofluorescence microscopy and subcellular fractionation. An L. major msrA null mutant, generated by targeted replacement of both chromosomal allelles, was viable in rich medium but was unable to reduce exogenous methionine sulfoxide when cultivated in the presence of this amino acid, indicating that msrA encodes a functional MsrA. The ΔmsrA mutant exhibited increased sensitivity to H(2O(2 compared to wild type parasites and was unable to proliferate normally in macrophages. Wild type sensitivity to H(2O(2 and infectivity in macrophages was restored by complementation of the mutant with a plasmid encoding MsrA. Unexpectedly, the ΔmsrA mutant was able to induce normal lesions in susceptible BALB/c indicating that this protein is not essential for pathogenesis in vivo. Our results suggest that Leishmania MsrA contributes to the anti-oxidative defences of these parasites, but that complementary oxidative defence mechansims are up-regulated in lesion amastigotes.

CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.

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Zhang, Yang; Li, Xiang-Xiang; Ma, Yuan; Xu, Jie; Zhao, Li-Na; Qian, Xue-Feng; Zhang, Xian-Feng; Shi, Jin-Fang; Han, Qing-Zhen

2017-12-04

Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.

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Inui, Toshio; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Sakamoto, Norihiro; Mette, Martin

2015-08-01

Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

HIV-1 Latency in Monocytes/Macrophages

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Amit Kumar

2014-04-01

Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

Parasitic infections of wild rabbits and hares

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Ilić Tamara

2014-01-01

Full Text Available The paper presents the most important parasitic infections of wild rabbits and hares, which harmful effect in this animal population is manifested as a gradual weakening of the immune system, reduction in fertility, weight loss and constant exhaustion. Order of Lagomorpha (hares or lagomorphs belongs to superorder of higher mammals which includes the family of rabbits (Leporidae which are represented in Europe as well as the family of whistleblowers (Ochotonidae which live only in North America and Northern regions of Asia. The most important representatives of Leporidae family are European hare (Lepus europeus and wild rabbit (Oryctolagus cuniculus. The most important endoparasitosis of hares and wild rabbits are: coccidiosis, encephalitozoonosis (nosemosis, toxoplasmosis, sarcocystosis, giardiasis, cryptosporidiosis, protostrongylosis, trichostrngylodosis, passalurosis, anoplocephalidosis, cysticercosis and fasciolosis. The most frequent ectoparasites of rabbits and wild hares are fleas, lice and ticks. Reduction in hare population, which is noticed in whole Europe including Serbia, is caused by changed living conditions, quantitatively and qualitatively insufficient nutrition, increased use of herbicides as well as various infectious diseases and the diseases of parasitic etiology. Since wild rabbits and hares pose a threat to health of domestic rabbits and people, knowledge of parasitic fauna of these wild animals is of extreme epizootiological and epidemiological importance.

Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

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Wim Grunewald

2009-01-01

Full Text Available Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

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Grunewald, Wim; Cannoot, Bernard; Friml, Jirí; Gheysen, Godelieve

2009-01-01

Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS) in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

Evaluation of the relationship between fungal infection, neutrophil leukocytes and macrophages in cervicovaginal smears: Light microscopic examination

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Sayeste Demirezen

2015-01-01

Conclusions: Our findings indicate that macrophages and neutrophils may play a determining role in host defense against fungal infection together, but neither yeast nor filamentous forms affect the presence of neutrophil leukocytes and macrophages. As a result of this, both yeast and filamentous forms may have pathogenic effects.

Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis

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Michell Stephen L

2011-01-01

Full Text Available Abstract Background Burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, B. thailandensis and B. oklahomensis, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (Galleria mellonella infection models. Results B. pseudomallei strains 576 and K96243, which have low median lethal dose (MLD values in mice, were able to replicate and induce cellular damage in macrophages and caused rapid death of G. mellonella. In contrast, B. pseudomallei strain 708a, which is attenuated in mice, showed reduced replication in macrophages, negligible cellular damage and was avirulent in G. mellonella larvae. B. thailandensis isolates were less virulent than B. pseudomallei in all of the models tested. However, we did record strain dependent differences. B. oklahomensis isolates were the least virulent isolates. They showed minimal ability to replicate in macrophages, were unable to evoke actin-based motility or to form multinucleated giant cells and were markedly attenuated in G. mellonella compared to B. thailandensis. Conclusions We have shown that the alternative infection models tested here, namely macrophages and Galleria mellonella, are able to distinguish between strains of B. pseudomallei, B. thailandensis and B. oklahomensis and that these differences reflect the observed virulence in murine infection models. Our results indicate that B. oklahomensis is the least pathogenic of the species investigated. They also show a correlation between isolates of B. thailandensis associated with human infection and virulence in macrophage and Galleria infection models.

Association of enteric parasitic infections with intestinal inflammation and permeability in asymptomatic infants of São Tomé Island.

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Garzón, Marisol; Pereira-da-Silva, Luis; Seixas, Jorge; Papoila, Ana Luísa; Alves, Marta; Ferreira, Filipa; Reis, Ana

2017-05-01

The cumulative effect of repeated asymptomatic enteric infections on intestinal barrier is not fully understood in infants. We aimed to evaluate the association between previous enteric parasitic infections and intestinal inflammation and permeability at 24-months of age, in asymptomatic infants of São Tomé Island. A subset of infants from a birth cohort, with intestinal parasite evaluations in at least four points of assessment, was eligible. Intestinal inflammatory response and permeability were assessed using fecal S100A12 and alpha-1-antitrypsin (A1AT), respectively. The cutoff parasitic infections explained variability of fecal biomarkers, after adjusting for potential confounders. Eighty infants were included. Giardia duodenalis and soil-transmitted helminths (STH) were the most frequent parasites. The median (interquartile range) levels were 2.87 μg/g (2.41-3.92) for S100A12 and 165.1 μg/g (66.0-275.6) for A1AT. Weak evidence of association was found between S100A12 levels and G. duodenalis (p = 0.080) and STH infections (p = 0.089), and between A1AT levels and parasitic infection of any etiology (p = 0.089), at 24-months of age. Significant associations between A1AT levels and wasting (p = 0.006) and stunting (p = 0.044) were found. Previous parasitic infections were not associated with fecal biomarkers at 24 months of age. To summarize, previous asymptomatic parasitic infections showed no association with intestinal barrier dysfunction. Notwithstanding, a tendency toward increased levels of the inflammatory biomarker was observed for current G. duodenalis and STH infections, and increased levels of the permeability biomarker were significantly associated with stunting and wasting.

Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

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Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

2014-03-21

It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.

Implications of malaria and intestinal parasitic co-infections among ...

African Journals Online (AJOL)

The prevalence of malaria and gastrointestinal parasitic infections in out-patients of Federal Medical Center (FMC) Owerri Specialist Hospital, was studied between the months of January and June 2004. A total of 1,200 patients made up of preschool children (400), school children (400) and adults (400) were enlisted for the ...

NSR-seq transcriptional profiling enables identification of a gene signature of Plasmodium falciparum parasites infecting children.

Science.gov (United States)

Vignali, Marissa; Armour, Christopher D; Chen, Jingyang; Morrison, Robert; Castle, John C; Biery, Matthew C; Bouzek, Heather; Moon, Wonjong; Babak, Tomas; Fried, Michal; Raymond, Christopher K; Duffy, Patrick E

2011-03-01

Malaria caused by Plasmodium falciparum results in approximately 1 million annual deaths worldwide, with young children and pregnant mothers at highest risk. Disease severity might be related to parasite virulence factors, but expression profiling studies of parasites to test this hypothesis have been hindered by extensive sequence variation in putative virulence genes and a preponderance of host RNA in clinical samples. We report here the application of RNA sequencing to clinical isolates of P. falciparum, using not-so-random (NSR) primers to successfully exclude human ribosomal RNA and globin transcripts and enrich for parasite transcripts. Using NSR-seq, we confirmed earlier microarray studies showing upregulation of a distinct subset of genes in parasites infecting pregnant women, including that encoding the well-established pregnancy malaria vaccine candidate var2csa. We also describe a subset of parasite transcripts that distinguished parasites infecting children from those infecting pregnant women and confirmed this observation using quantitative real-time PCR and mass spectrometry proteomic analyses. Based on their putative functional properties, we propose that these proteins could have a role in childhood malaria pathogenesis. Our study provides proof of principle that NSR-seq represents an approach that can be used to study clinical isolates of parasites causing severe malaria syndromes as well other blood-borne pathogens and blood-related diseases.

NSR-seq transcriptional profiling enables identification of a gene signature of Plasmodium falciparum parasites infecting children

Science.gov (United States)

Vignali, Marissa; Armour, Christopher D.; Chen, Jingyang; Morrison, Robert; Castle, John C.; Biery, Matthew C.; Bouzek, Heather; Moon, Wonjong; Babak, Tomas; Fried, Michal; Raymond, Christopher K.; Duffy, Patrick E.

2011-01-01

Malaria caused by Plasmodium falciparum results in approximately 1 million annual deaths worldwide, with young children and pregnant mothers at highest risk. Disease severity might be related to parasite virulence factors, but expression profiling studies of parasites to test this hypothesis have been hindered by extensive sequence variation in putative virulence genes and a preponderance of host RNA in clinical samples. We report here the application of RNA sequencing to clinical isolates of P. falciparum, using not-so-random (NSR) primers to successfully exclude human ribosomal RNA and globin transcripts and enrich for parasite transcripts. Using NSR-seq, we confirmed earlier microarray studies showing upregulation of a distinct subset of genes in parasites infecting pregnant women, including that encoding the well-established pregnancy malaria vaccine candidate var2csa. We also describe a subset of parasite transcripts that distinguished parasites infecting children from those infecting pregnant women and confirmed this observation using quantitative real-time PCR and mass spectrometry proteomic analyses. Based on their putative functional properties, we propose that these proteins could have a role in childhood malaria pathogenesis. Our study provides proof of principle that NSR-seq represents an approach that can be used to study clinical isolates of parasites causing severe malaria syndromes as well other blood-borne pathogens and blood-related diseases. PMID:21317536

Infection with HIV and intestinal parasites among street dwellers in Gondar city, northwest Ethiopia.

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Moges, Feleke; Kebede, Yenew; Kassu, Afework; Degu, Getu; Tiruneh, Moges; Gedefaw, Molla

2006-12-01

In Ethiopia human immunodeficiency virus (HIV) infection is a major health and socioeconomic problem. Sex workers, youth, and mobile populations all show increasing prevalence of HIV. However, there is currently no information about the seroprevalence of HIV and the knowledge of HIV among street dwellers in the country. To fill this gap, 404 street dwellers residing in Gondar, northwest Ethiopia, were included in this cross-sectional study. Socio-demographic data, factors that prompted the subjects to become street dwellers, and their knowledge about HIV were all assessed using a structured questionnaire. Stool samples for diagnosis of intestinal parasites and venous blood for HIV antibody testing were collected and processed following standard procedures. Poverty-associated movement to urban areas in search of work was reported as a major factor that forced them to live in the streets, followed by divorce, family death, and addiction and peer pressure. One or more intestinal parasites were found in 67.6% of the street dwellers. Multiple parasitic infections were detected in 27.7%. The prevalence of HIV in the street dwellers was 6.9%. Fifty-nine (16.6%) participants responded that HIV can be transmitted by eating food together. Seventy-three (18%) believed an infected needle cannot transmit HIV, while 51 (12.6%) said HIV can be transmitted by hand shaking. One hundred ninety-two (47.5%) responded that antiretroviral therapy will not prolong the life of HIV-infected individuals. In summary, the prevalence of HIV and intestinal parasitic infection was quite high among street dwellers in Gondar. Therefore, strategies to control HIV and other infectious diseases should include this group, and regular mass deworming may help to reduce the burden of infection.

Infection by Intestinal Parasites, Stunting and Anemia in School-Aged Children from Southern Angola.

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Dinamene Oliveira

Full Text Available Intestinal parasites are responsible for morbidity in children worldwide, especially in low income countries. In the present study we determine the prevalence of intestinal parasites and explore its association with anemia and stunting in school-aged children.A cross-sectional study was conducted from September to October 2010 enrolling 328 children attending the primary school in Lubango, the second largest city after the capital Luanda. Stool samples were collected for parasite detection through microscopy and molecular identification of Entamoeba histolytica and Entamoeba dispar. Stunting was assessed using the z-scores of height for age and hemoglobin concentration was determined using a portable hemoglobin analyzing system.The global prevalence of pathogenic intestinal parasites was 44.2%, the most common being Ascaris lumbricoides (22.0%, Giardia lamblia (20.1% and Hymenolepis nana (8.8%. Molecular detection revealed that 13.1% of the children carried E. dispar and 0.3% were infected with E. histolytica. The prevalence of stunting (mild to severe was 41.5%. Stunting was more frequent in older children (p = 0.006, OR = 1.886, while anemia was more frequent in younger children (p = 0.005, OR = 2.210. The prevalence of anemia was 21.6%, and we found a significant association with infection by H. nana (p = 0.031, OR = 2.449.This is one of the few published studies reporting intestinal parasites infection, nutritional status and anemia in children from Angola. Furthermore, the present work highlights the importance of regular intestinal parasites screening in children.

HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages

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Purcell Damian FJ

2008-02-01

Full Text Available Abstract Background Macrophages are important targets and long-lived reservoirs of HIV-1, which are not cleared of infection by currently available treatments. In the primary monocyte-derived macrophage model of infection, replication is initially productive followed by a decline in virion output over ensuing weeks, coincident with a decrease in the levels of the essential viral transactivator protein Tat. We investigated two possible mechanisms in macrophages for regulation of viral replication, which appears to be primarily regulated at the level of tat mRNA: 1 differential mRNA stability, used by cells and some viruses for the rapid regulation of gene expression and 2 control of HIV-1 alternative splicing, which is essential for optimal viral replication. Results Following termination of transcription at increasing times after infection in macrophages, we found that tat mRNA did indeed decay more rapidly than rev or nef mRNA, but with similar kinetics throughout infection. In addition, tat mRNA decayed at least as rapidly in peripheral blood lymphocytes. Expression of cellular splicing factors in uninfected and infected macrophage cultures from the same donor showed an inverse pattern over time between enhancing factors (members of the SR family of RNA binding proteins and inhibitory factors (members of the hnRNP family. While levels of the SR protein SC35 were greatly up-regulated in the first week or two after infection, hnRNPs of the A/B and H groups were down-regulated. Around the peak of virus production in each culture, SC35 expression declined to levels in uninfected cells or lower, while the hnRNPs increased to control levels or above. We also found evidence for increased cytoplasmic expression of SC35 following long-term infection. Conclusion While no evidence of differential regulation of tat mRNA decay was found in macrophages following HIV-1 infection, changes in the balance of cellular splicing factors which regulate alternative

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