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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 Schistosoma mansoni. Although the impo...

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Autores principales: Ndlovu, Hlumani, Nono, Justin Komguep, Abdel Aziz, Nada, Nieuwenhuizen, Natalie Eva, Brombacher, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305417/
https://www.ncbi.nlm.nih.gov/pubmed/30619289
http://dx.doi.org/10.3389/fimmu.2018.02928
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author Ndlovu, Hlumani
Nono, Justin Komguep
Abdel Aziz, Nada
Nieuwenhuizen, Natalie Eva
Brombacher, Frank
author_facet Ndlovu, Hlumani
Nono, Justin Komguep
Abdel Aziz, Nada
Nieuwenhuizen, Natalie Eva
Brombacher, Frank
author_sort Ndlovu, Hlumani
collection PubMed
description 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 Schistosoma mansoni. 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. To address this, we examined B cell-specific IL-4Rα-deficient (mb1(cre)IL-4Rα(−/lox)) mice in three experimental models of schistosomiasis: high-dose (100 cercariae), low dose (30 cercariae), and a synchronous egg challenge. In the high dose model, we found that mice deficient in IL-4Rα-expressing B cells were more susceptible to acute schistosomiasis than B cell-deficient (μMT) mice, succumbing to infection at the acute stage whereas μMT mice survived until the chronic stage. An S. mansoni egg challenge model demonstrated that deleting IL-4Rα expression specifically on B cells resulted in increased lung granulomatous pathology, suggesting a role for this B cell subset in controlling granulomatous pathology. In agreement with this, a low dose model of schistosomiasis—which mimics the course of clinical chronic disease—demonstrated that depleting IL-4Rα-expressing B cells in mb1(cre)IL-4Rα(−/lox) mice considerably impaired the host ability to down-modulate granulomatous inflammation in the liver and gut during chronic schistosomiasis. Taken together, our findings indicate that within the B cell compartment, IL-4Rα-expressing B cells in particular down-modulate the deleterious egg-driven tissue granulomatous inflammation to enable host survival during schistosomiasis in mice.
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spelling pubmed-63054172019-01-07 Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis Ndlovu, Hlumani Nono, Justin Komguep Abdel Aziz, Nada Nieuwenhuizen, Natalie Eva Brombacher, Frank Front Immunol Immunology 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 Schistosoma mansoni. 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. To address this, we examined B cell-specific IL-4Rα-deficient (mb1(cre)IL-4Rα(−/lox)) mice in three experimental models of schistosomiasis: high-dose (100 cercariae), low dose (30 cercariae), and a synchronous egg challenge. In the high dose model, we found that mice deficient in IL-4Rα-expressing B cells were more susceptible to acute schistosomiasis than B cell-deficient (μMT) mice, succumbing to infection at the acute stage whereas μMT mice survived until the chronic stage. An S. mansoni egg challenge model demonstrated that deleting IL-4Rα expression specifically on B cells resulted in increased lung granulomatous pathology, suggesting a role for this B cell subset in controlling granulomatous pathology. In agreement with this, a low dose model of schistosomiasis—which mimics the course of clinical chronic disease—demonstrated that depleting IL-4Rα-expressing B cells in mb1(cre)IL-4Rα(−/lox) mice considerably impaired the host ability to down-modulate granulomatous inflammation in the liver and gut during chronic schistosomiasis. Taken together, our findings indicate that within the B cell compartment, IL-4Rα-expressing B cells in particular down-modulate the deleterious egg-driven tissue granulomatous inflammation to enable host survival during schistosomiasis in mice. Frontiers Media S.A. 2018-12-18 /pmc/articles/PMC6305417/ /pubmed/30619289 http://dx.doi.org/10.3389/fimmu.2018.02928 Text en Copyright © 2018 Ndlovu, Nono, Abdel Aziz, Nieuwenhuizen and Brombacher. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ndlovu, Hlumani
Nono, Justin Komguep
Abdel Aziz, Nada
Nieuwenhuizen, Natalie Eva
Brombacher, Frank
Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis
title Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis
title_full Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis
title_fullStr Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis
title_full_unstemmed Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis
title_short Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis
title_sort interleukin-4 receptor alpha expressing b cells are essential to down-modulate host granulomatous inflammation during schistosomasis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305417/
https://www.ncbi.nlm.nih.gov/pubmed/30619289
http://dx.doi.org/10.3389/fimmu.2018.02928
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