Cysteinyl leukotriene receptor-1 as a potential target for host-directed therapy during chronic schistosomiasis in murine model.

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas.

Harnessing Schistosoma-associated metabolite changes in the human host to identify biomarkers of infection and morbidity: Where are we and what should we do next?

Schistosomiasis is the second most widespread parasitic disease affecting humans. A key component of today's infection control measures is the diagnosis and monitoring of infection, informing individual- and community-level treatment. However, newly acquired infections and/or low parasite burden are still difficult to diagnose reliably.

Plasma IL-33 levels and immune activation in HIV-TB coinfection: a cross-sectional study in Yaoundé, Cameroon.

Introduction: HIV-1 and Mtb are characterized by immune activation and unbalances production of cytokines, but the expression of IL33 in HIV/TB coinfection remain understudied. This study aimed to evaluate the level of IL-33 in plasma of HIV and M. tuberculosis (HIV/TB) coinfected patients compared to patients with respective mono infections in Yaoundé.

Schistosoma mansoni infection induces plasmablast and plasma cell death in the bone marrow and accelerates the decline of host vaccine responses.

Schistosomiasis is a potentially lethal parasitic disease that profoundly impacts systemic immune function in chronically infected hosts through mechanisms that remain unknown. Given the immunoregulatory dysregulation experienced in infected individuals, this study examined the impact of chronic schistosomiasis on the sustainability of vaccine-induced immunity in both children living in endemic areas and experimental infections in mice. Data show that chronic Schistosoma mansoni infection impaired the persistence of vaccine specific antibody responses in poliovirus-vaccinated humans and mice.

Praziquantel Treatment of Infected Mice Renders Them Less Susceptible to Reinfection.

Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection.

IL-4i1 Regulation of Immune Protection During Mycobacterium tuberculosis Infection.

Background: Interleukin 4 (IL-4i1)-induced gene 1 encodes L-phenylalanine oxidase that catabolizes phenylalanine into phenylpyruvate. IL-4i1 is mainly expressed by antigen-presenting cells (APCs), inhibits T-cell proliferation, regulates B-cell activation, modulates T cell responses, and drives macrophage polarization, but its role in bacterial infections is understudied.

Methods: We evaluated IL-4i1 deletion in macrophages and mice on infection with virulent H37Rv and W-Beijing lineage hypervirulent HN878 Mycobacterium tuberculosis (Mtb) strains.

Influence of schistosomiasis on host vaccine responses.

Schistosomiasis is a debilitating helminthiasis which commonly establishes as a chronic infection in people from endemic areas. As a potent modulator of the host immune response, the Schistosoma parasite and its associated products can directly interfere with its host's ability to mount adequate immune responses to unrelated antigens. As a result, increased attention is gathering on studies assessing the influence of helminths, particularly the causal agent of schistosomiasis, on host responsiveness to vaccines.

Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models.

Tissue fibrosis underlies the majority of human mortality to date with close to half of all reported deaths having a fibrotic etiology. The progression of fibrosis is very complex and reputed irreversible once established. Although some preventive options are being reported, therapeutic options are still scarce and in very high demand, given the rise of diseases linked to fibroproliferative disorders.

Expansion of Host Regulatory T Cells by Secreted Products of the Tapeworm .

Background: Alveolar echinococcosis (AE), caused by the metacestode larval stage of the fox-tapeworm , is a chronic zoonosis associated with significant modulation of the host immune response. A role of regulatory T-cells (Treg) in generating an immunosuppressive environment around the metacestode during chronic disease has been reported, but the molecular mechanisms of Treg induction by , particularly parasite immunoregulatory factors involved, remain elusive so far.

Methodology/principal Findings: We herein demonstrate that excretory/secretory (E/S) products of the metacestode promote the formation of Foxp3 Treg from CD4 T-cells in a TGF-β-dependent manner, given that this effect was abrogated by treatment with antibody to mammalian TGF-β.

An ultrasound-based referential of body height-adjusted normal liver organometry in school children from Bokito in rural Cameroon.

The grading system for ultrasonographic assessment of Schistosoma mansoni morbidity is crucial for evaluation of control programs. This requires prior definition of normal liver organometric ranges in the population from the endemic area. A cross-sectional study was conducted in a S.

Negative Association of Interleukin-33 Plasma Levels and Schistosomiasis Infection in a Site of Polyparasitism in Rural Cameroon.

This study aimed to investigate the association of plasma levels of IL-33, a mucosal alarmin known to elicit type-2 immunity, with infection and liver fibrosis profiles of school children from an endemic area for , malaria and hepatitis (B & C) in rural Cameroon. A cross-sectional study enrolling schoolchildren from 5 public schools was conducted. Single schistosomiasis, malaria and hepatitis infections or co-infections were assessed by kato katz, microscopy, and rapid diagnostic tests, respectively.

Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis.

Schistosomiasis (bilharzia) is a parasitic helminth disease that can cause severe inflammatory pathology leading to organ damage in humans. Failure of the host to regulate egg-driven granulomatous inflammation causes host morbidity during chronic infection with . Although the importance of B cells in regulating pathology during chronic infection has been well defined, the specific contribution of IL-4Rα-expressing B cells is still unknown.

Host Regulators of Liver Fibrosis During Human Schistosomiasis.

Liver fibrosis is a wound-healing process purposely aimed at restoring organ integrity after severe injury caused by autoimmune reactions, mechanical stress or infections. The uncontrolled solicitation of this process is pathogenic and a pathognomonic feature of diseases like hepatosplenic schistosomiasis where exacerbated liver fibrosis is centrally positioned among the drivers of the disease morbidity and mortality. Intriguingly, however, liver fibrosis occurs and progresses dissimilarly in schistosomiasis-diseased individuals with the same egg burden and biosocial features including age, duration of residence in the endemic site and gender.

Batf2 differentially regulates tissue immunopathology in Type 1 and Type 2 diseases.

Basic leucine zipper transcription factor 2 (Batf2) activation is detrimental in Type 1-controlled infectious diseases, demonstrated during infection with Mycobacterium tuberculosis (Mtb) and Listeria monocytogenes Lm. In Batf2-deficient mice (Batf2), infected with Mtb or Lm, mice survived and displayed reduced tissue pathology compared to infected control mice. Indeed, pulmonary inflammatory macrophage recruitment, pro-inflammatory cytokines and immune effectors were also decreased during tuberculosis.

IL-4Rα-expressing CD11c cells contribute to driving optimal cellular responses during Schistosoma mansoni infection in mice.

Development of IL-4 receptor alpha (IL-4Rα)-dependent cellular immunity regulates host protection against acute schistosomiasis. In this study, we investigated the importance of IL-4Rα-expressing CD11c cells in driving the development of optimal cellular responses to Schistosoma mansoni infection by using CD11c IL-4Rα BALB/c mice, which lacked IL-4Rα expression on dendritic cells and alveolar macrophages. Abrogation of IL-4Rα expression on CD11c cells affected activation of CD4 T cells, resulting in reduced numbers of effector CD4 T cells and impaired production of Th1 and Th2 cytokines by CD4 T cells ex vivo.

The Foxp3+ regulatory T-cell population requires IL-4Rα signaling to control inflammation during helminth infections.

Forkhead box P3 (Foxp3+) regulatory T (Treg)-cell function is controlled by environmental cues of which cytokine-mediated signaling is a dominant component. In vivo, interleukin-4 (IL-4)-mediated signaling via IL-4 receptor alpha (IL-4Rα) mediates Treg cell transdifferentiation into ex-Foxp3 T helper 2 (Th2) or T helper 17 (Th17) cells. However, IL-4-mediated signaling also reinforces the Foxp3 Treg compartment in vitro.

Schistosomiasis Burden and Its Association With Lower Measles Vaccine Responses in School Children From Rural Cameroon.

Schistosomiasis is debilitating and reported to impair immune responsiveness of infected hosts. In Cameroon, mass drug administration (MDA) is used in schoolchildren to reduce transmission of and . The effects of MDA and the impact of schistosomiasis on the titers of antibodies in vaccinated children have been poorly studied.

IL-4-producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases.

Interleukin-4 (IL-4)-induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite , while conferring immunity to the intestinal trematode Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice (IL-4Rα) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to infection. We further demonstrate that the absence of IL-4Rα signaling on B cells exacerbated -induced mortality and pathology in BALB/c mice, due to a diminished type 2 immune response.

Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha.

Interleukin-4 receptor (IL-4Rα) is critical for the initiation of type-2 immune responses and implicated in the pathogenesis of experimental schistosomiasis. IL-4Rα mediated type-2 responses are critical for the control of pathology during acute schistosomiasis. However, type-2 responses tightly associate with fibrogranulomatous inflammation that drives host pathology during chronic schistosomiasis.

Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection.

There is currently no vaccine against parasitic nematodes and the knowledge on the mechanisms by which protective immunity against this class of parasites is achieved is continuously expanding. Nematode parasites trigger a host protective type 2 immune response via interleukin-4 receptor alpha (IL-4Rα). Despite this central role, it is not known whether IL-4Rα has a role in maintaining host type 2 immune responses following polarization.

IL-13-Mediated Regulation of Learning and Memory.

The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13-deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning.

Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions.

Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M.

In vitro culture of Mesocestoides corti metacestodes and isolation of immunomodulatory excretory-secretory products.

Cestode-mediated diseases hold the interesting feature of persisting metacestode larvae dwelling within the host tissues, in the midst of the immune response. Excretory-secretory (ES) products of the metacestode larval stage modulate the host immune response and modify the outcome of the disease. Therefore, isolation and analysis of axenic metacestode ES products are crucial to study their properties.