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 ass...
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ftdoajarticles:oai:doaj.org/article:cdf2a8b7ff8441ccaf05d2fc196e9ce4 2023-05-15T15:08:18+02:00 Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. Justin Komguep Nono Hlumani Ndlovu Nada Abdel Aziz Thabo Mpotje Lerato Hlaka Frank Brombacher 2017-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005861 https://doaj.org/article/cdf2a8b7ff8441ccaf05d2fc196e9ce4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5578697?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005861 https://doaj.org/article/cdf2a8b7ff8441ccaf05d2fc196e9ce4 PLoS Neglected Tropical Diseases, Vol 11, Iss 8, p e0005861 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005861 2022-12-31T15:58:38Z 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. To address such controversy on the role of IL-4Rα, we generated a novel inducible IL-4Rα-deficient mouse model that allows for temporal knockdown of il-4rα gene after oral administration of Tamoxifen. Interrupting IL-4Rα mediated signaling during the acute phase impaired the development of protective type-2 immune responses, leading to rapid weight loss and premature death, confirming a protective role of IL-4Rα during acute schistosomiasis. Conversely, IL-4Rα removal at the chronic phase of schistosomiasis ameliorated the pathological fibro-granulomatous pathology and reversed liver scarification without affecting the host fitness. This amelioration of the morbidity was accompanied by a reduced Th2 response and increased frequencies of FoxP3+ Tregs and CD1dhiCD5+ Bregs. Collectively, these data demonstrate that IL-4Rα mediated signaling has two opposing functions during experimental schistosomiasis depending on the stage of advancement of the disease and indicate that interrupting IL-4Rα mediated signaling is a viable therapeutic strategy to ameliorate liver fibroproliferative pathology in diseases like chronic schistosomiasis. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 8 e0005861 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Justin Komguep Nono Hlumani Ndlovu Nada Abdel Aziz Thabo Mpotje Lerato Hlaka Frank Brombacher Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. To address such controversy on the role of IL-4Rα, we generated a novel inducible IL-4Rα-deficient mouse model that allows for temporal knockdown of il-4rα gene after oral administration of Tamoxifen. Interrupting IL-4Rα mediated signaling during the acute phase impaired the development of protective type-2 immune responses, leading to rapid weight loss and premature death, confirming a protective role of IL-4Rα during acute schistosomiasis. Conversely, IL-4Rα removal at the chronic phase of schistosomiasis ameliorated the pathological fibro-granulomatous pathology and reversed liver scarification without affecting the host fitness. This amelioration of the morbidity was accompanied by a reduced Th2 response and increased frequencies of FoxP3+ Tregs and CD1dhiCD5+ Bregs. Collectively, these data demonstrate that IL-4Rα mediated signaling has two opposing functions during experimental schistosomiasis depending on the stage of advancement of the disease and indicate that interrupting IL-4Rα mediated signaling is a viable therapeutic strategy to ameliorate liver fibroproliferative pathology in diseases like chronic schistosomiasis. |
format |
Article in Journal/Newspaper |
author |
Justin Komguep Nono Hlumani Ndlovu Nada Abdel Aziz Thabo Mpotje Lerato Hlaka Frank Brombacher |
author_facet |
Justin Komguep Nono Hlumani Ndlovu Nada Abdel Aziz Thabo Mpotje Lerato Hlaka Frank Brombacher |
author_sort |
Justin Komguep Nono |
title |
Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
title_short |
Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
title_full |
Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
title_fullStr |
Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
title_full_unstemmed |
Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
title_sort |
host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005861 https://doaj.org/article/cdf2a8b7ff8441ccaf05d2fc196e9ce4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 8, p e0005861 (2017) |
op_relation |
http://europepmc.org/articles/PMC5578697?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005861 https://doaj.org/article/cdf2a8b7ff8441ccaf05d2fc196e9ce4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005861 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
8 |
container_start_page |
e0005861 |
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