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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-4...

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Autores principales: Nono, Justin Komguep, Ndlovu, Hlumani, Abdel Aziz, Nada, Mpotje, Thabo, Hlaka, Lerato, Brombacher, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501681/
https://www.ncbi.nlm.nih.gov/pubmed/28651009
http://dx.doi.org/10.1371/journal.pntd.0005675
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author Nono, Justin Komguep
Ndlovu, Hlumani
Abdel Aziz, Nada
Mpotje, Thabo
Hlaka, Lerato
Brombacher, Frank
author_facet Nono, Justin Komguep
Ndlovu, Hlumani
Abdel Aziz, Nada
Mpotje, Thabo
Hlaka, Lerato
Brombacher, Frank
author_sort Nono, Justin Komguep
collection PubMed
description 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. To determine the role of IL-4Rα after polarization, we used a recently established strain of rosaCreER(T2-/+)IL-4Rα(-/Lox) mice where il4rα gene deletion can be temporally controlled. We show that sustained expression of IL-4Rα is required for the maintenance of type 2 immune responses and protective immunity following interruption after polarization with Nippostrongylus brasiliensis primary infection. Moreover, we show by temporal deletion of IL-4Rα prior to secondary infection with N. brasiliensis that signaling via this receptor drives more efficient recall of type 2 immune responses and clearance of the parasites. Together, this study demonstrates that sustained IL-4Rα mediated signaling is required for the maintenance of anti-nematode type 2 immune responses, describing a novel function for IL-4Rα that is distinct from its role in immune polarization.
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spelling pubmed-55016812017-07-25 Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection Nono, Justin Komguep Ndlovu, Hlumani Abdel Aziz, Nada Mpotje, Thabo Hlaka, Lerato Brombacher, Frank PLoS Negl Trop Dis Research Article 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. To determine the role of IL-4Rα after polarization, we used a recently established strain of rosaCreER(T2-/+)IL-4Rα(-/Lox) mice where il4rα gene deletion can be temporally controlled. We show that sustained expression of IL-4Rα is required for the maintenance of type 2 immune responses and protective immunity following interruption after polarization with Nippostrongylus brasiliensis primary infection. Moreover, we show by temporal deletion of IL-4Rα prior to secondary infection with N. brasiliensis that signaling via this receptor drives more efficient recall of type 2 immune responses and clearance of the parasites. Together, this study demonstrates that sustained IL-4Rα mediated signaling is required for the maintenance of anti-nematode type 2 immune responses, describing a novel function for IL-4Rα that is distinct from its role in immune polarization. Public Library of Science 2017-06-26 /pmc/articles/PMC5501681/ /pubmed/28651009 http://dx.doi.org/10.1371/journal.pntd.0005675 Text en © 2017 Nono et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nono, Justin Komguep
Ndlovu, Hlumani
Abdel Aziz, Nada
Mpotje, Thabo
Hlaka, Lerato
Brombacher, Frank
Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection
title Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection
title_full Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection
title_fullStr Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection
title_full_unstemmed Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection
title_short Interleukin-4 receptor alpha is still required after Th2 polarization for the maintenance and the recall of protective immunity to Nematode infection
title_sort interleukin-4 receptor alpha is still required after th2 polarization for the maintenance and the recall of protective immunity to nematode infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501681/
https://www.ncbi.nlm.nih.gov/pubmed/28651009
http://dx.doi.org/10.1371/journal.pntd.0005675
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