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Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis
Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389433/ https://www.ncbi.nlm.nih.gov/pubmed/34398890 http://dx.doi.org/10.1371/journal.pntd.0009696 |
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author | Yu, Yanxiong Wang, Junling Wang, Xiaohong Gu, Pan Lei, Zhigang Tang, Rui Wei, Chuan Xu, Lei Wang, Chun Chen, Ying Pu, Yanan Qi, Xin Yu, Beibei Chen, Xiaojun Zhu, Jifeng Li, Yalin Zhang, Zhijie Zhou, Sha Su, Chuan |
author_facet | Yu, Yanxiong Wang, Junling Wang, Xiaohong Gu, Pan Lei, Zhigang Tang, Rui Wei, Chuan Xu, Lei Wang, Chun Chen, Ying Pu, Yanan Qi, Xin Yu, Beibei Chen, Xiaojun Zhu, Jifeng Li, Yalin Zhang, Zhijie Zhou, Sha Su, Chuan |
author_sort | Yu, Yanxiong |
collection | PubMed |
description | Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of the host. Schistosome eggs induce M2 macrophages-rich granulomas and these M2 macrophages play critical roles in the maintenance of granuloma and subsequent fibrosis. Reactive oxygen species (ROS), which are highly produced by stimulated macrophages during infection and necessary for the differentiation of M2 macrophages, are massively distributed around deposited eggs in the liver. However, whether ROS are induced by schistosome eggs to subsequently promote M2 macrophage differentiation, and the possible underlying mechanisms as well, remain to be clarified during S. japonicum infection. Herein, we observed that extensive expression of ROS in the liver of S. japonicum-infected mice. Injection of ROS inhibitor in infected mice resulted in reduced hepatic granulomatous responses and fibrosis. Further investigations revealed that inhibition of ROS production in S. japonicum-infected mice reduces the differentiation of M2, accompanied by increased M1 macrophage differentiation. Finally, we proved that S. japonicum egg antigens (SEA) induce a high level of ROS production via both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and mitochondria in macrophages. Our study may help to better understand the mechanism of schistosomiasis japonica-induced hepatic pathology and contribute to the development of potential therapeutic strategies by interfering with ROS production. |
format | Online Article Text |
id | pubmed-8389433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83894332021-08-27 Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis Yu, Yanxiong Wang, Junling Wang, Xiaohong Gu, Pan Lei, Zhigang Tang, Rui Wei, Chuan Xu, Lei Wang, Chun Chen, Ying Pu, Yanan Qi, Xin Yu, Beibei Chen, Xiaojun Zhu, Jifeng Li, Yalin Zhang, Zhijie Zhou, Sha Su, Chuan PLoS Negl Trop Dis Research Article Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of the host. Schistosome eggs induce M2 macrophages-rich granulomas and these M2 macrophages play critical roles in the maintenance of granuloma and subsequent fibrosis. Reactive oxygen species (ROS), which are highly produced by stimulated macrophages during infection and necessary for the differentiation of M2 macrophages, are massively distributed around deposited eggs in the liver. However, whether ROS are induced by schistosome eggs to subsequently promote M2 macrophage differentiation, and the possible underlying mechanisms as well, remain to be clarified during S. japonicum infection. Herein, we observed that extensive expression of ROS in the liver of S. japonicum-infected mice. Injection of ROS inhibitor in infected mice resulted in reduced hepatic granulomatous responses and fibrosis. Further investigations revealed that inhibition of ROS production in S. japonicum-infected mice reduces the differentiation of M2, accompanied by increased M1 macrophage differentiation. Finally, we proved that S. japonicum egg antigens (SEA) induce a high level of ROS production via both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and mitochondria in macrophages. Our study may help to better understand the mechanism of schistosomiasis japonica-induced hepatic pathology and contribute to the development of potential therapeutic strategies by interfering with ROS production. Public Library of Science 2021-08-16 /pmc/articles/PMC8389433/ /pubmed/34398890 http://dx.doi.org/10.1371/journal.pntd.0009696 Text en © 2021 Yu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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 Yu, Yanxiong Wang, Junling Wang, Xiaohong Gu, Pan Lei, Zhigang Tang, Rui Wei, Chuan Xu, Lei Wang, Chun Chen, Ying Pu, Yanan Qi, Xin Yu, Beibei Chen, Xiaojun Zhu, Jifeng Li, Yalin Zhang, Zhijie Zhou, Sha Su, Chuan Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
title | Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
title_full | Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
title_fullStr | Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
title_full_unstemmed | Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
title_short | Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
title_sort | schistosome eggs stimulate reactive oxygen species production to enhance m2 macrophage differentiation and promote hepatic pathology in schistosomiasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389433/ https://www.ncbi.nlm.nih.gov/pubmed/34398890 http://dx.doi.org/10.1371/journal.pntd.0009696 |
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