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Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis
Schistosomiasis is endemic to many regions of the world and affects approximately 200 million people. Conventional adaptive T cell responses are considered to be the primary contributors to the pathogenesis of Schistosoma japonicum infection, leading to liver granuloma and fibrosis. However, the fun...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307705/ https://www.ncbi.nlm.nih.gov/pubmed/30589840 http://dx.doi.org/10.1371/journal.pntd.0007000 |
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author | Gong, Wenci Huang, Fengjuan Sun, Lei Yu, Aiping Zhang, Xiaofan Xu, Yuxin Shen, Yujuan Cao, Jianping |
author_facet | Gong, Wenci Huang, Fengjuan Sun, Lei Yu, Aiping Zhang, Xiaofan Xu, Yuxin Shen, Yujuan Cao, Jianping |
author_sort | Gong, Wenci |
collection | PubMed |
description | Schistosomiasis is endemic to many regions of the world and affects approximately 200 million people. Conventional adaptive T cell responses are considered to be the primary contributors to the pathogenesis of Schistosoma japonicum infection, leading to liver granuloma and fibrosis. However, the functional polarization of macrophages and the associated underlying molecular mechanisms during the pathogenesis of schistosomiasis remains unknown. In the present study, we found that excretory-secretory (ES) antigens derived from S. japonicum eggs can activate macrophages, which exhibit an M2b polarization. Furthermore, ES antigen-induced M2b polarization was found to be dependent on enhanced NF-κB signaling mediated by the MyD88/MAPK pathway in a TLR2-dependent manner. In addition, the cytokine profile of the liver macrophages from wild-type-infected mice are quite distinct from those found in TLR2 knockout-infected mice by quantitative PCR analysis. More importantly, the size of granuloma and the severity of the fibrosis in the livers of TLR2(-/-) mice were significantly reduced compared to that in WT mice. Our findings reveal a novel role for M2b polarization in the pathogenesis of schistosome infection. |
format | Online Article Text |
id | pubmed-6307705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-63077052019-01-08 Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis Gong, Wenci Huang, Fengjuan Sun, Lei Yu, Aiping Zhang, Xiaofan Xu, Yuxin Shen, Yujuan Cao, Jianping PLoS Negl Trop Dis Research Article Schistosomiasis is endemic to many regions of the world and affects approximately 200 million people. Conventional adaptive T cell responses are considered to be the primary contributors to the pathogenesis of Schistosoma japonicum infection, leading to liver granuloma and fibrosis. However, the functional polarization of macrophages and the associated underlying molecular mechanisms during the pathogenesis of schistosomiasis remains unknown. In the present study, we found that excretory-secretory (ES) antigens derived from S. japonicum eggs can activate macrophages, which exhibit an M2b polarization. Furthermore, ES antigen-induced M2b polarization was found to be dependent on enhanced NF-κB signaling mediated by the MyD88/MAPK pathway in a TLR2-dependent manner. In addition, the cytokine profile of the liver macrophages from wild-type-infected mice are quite distinct from those found in TLR2 knockout-infected mice by quantitative PCR analysis. More importantly, the size of granuloma and the severity of the fibrosis in the livers of TLR2(-/-) mice were significantly reduced compared to that in WT mice. Our findings reveal a novel role for M2b polarization in the pathogenesis of schistosome infection. Public Library of Science 2018-12-27 /pmc/articles/PMC6307705/ /pubmed/30589840 http://dx.doi.org/10.1371/journal.pntd.0007000 Text en © 2018 Gong 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 Gong, Wenci Huang, Fengjuan Sun, Lei Yu, Aiping Zhang, Xiaofan Xu, Yuxin Shen, Yujuan Cao, Jianping Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
title | Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
title_full | Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
title_fullStr | Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
title_full_unstemmed | Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
title_short | Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
title_sort | toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307705/ https://www.ncbi.nlm.nih.gov/pubmed/30589840 http://dx.doi.org/10.1371/journal.pntd.0007000 |
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