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...

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Autores principales:	Yanxiong Yu, Junling Wang, Xiaohong Wang, Pan Gu, Zhigang Lei, Rui Tang, Chuan Wei, Lei Xu, Chun Wang, Ying Chen, Yanan Pu, Xin Qi, Beibei Yu, Xiaojun Chen, Jifeng Zhu, Yalin Li, Zhijie Zhang, Sha Zhou, Chuan Su
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/b8244d49c5c545d286106ed6d5c6c9e6
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spelling	oai:doaj.org-article:b8244d49c5c545d286106ed6d5c6c9e62021-12-02T20:24:17ZSchistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis.1935-27271935-273510.1371/journal.pntd.0009696https://doaj.org/article/b8244d49c5c545d286106ed6d5c6c9e62021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009696https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Schistosomiasis 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.Yanxiong YuJunling WangXiaohong WangPan GuZhigang LeiRui TangChuan WeiLei XuChun WangYing ChenYanan PuXin QiBeibei YuXiaojun ChenJifeng ZhuYalin LiZhijie ZhangSha ZhouChuan SuPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 8, p e0009696 (2021)
institution	DOAJ
collection	DOAJ
language	EN
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 Yanxiong Yu Junling Wang Xiaohong Wang Pan Gu Zhigang Lei Rui Tang Chuan Wei Lei Xu Chun Wang Ying Chen Yanan Pu Xin Qi Beibei Yu Xiaojun Chen Jifeng Zhu Yalin Li Zhijie Zhang Sha Zhou Chuan Su Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis.
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	article
author	Yanxiong Yu Junling Wang Xiaohong Wang Pan Gu Zhigang Lei Rui Tang Chuan Wei Lei Xu Chun Wang Ying Chen Yanan Pu Xin Qi Beibei Yu Xiaojun Chen Jifeng Zhu Yalin Li Zhijie Zhang Sha Zhou Chuan Su
author_facet	Yanxiong Yu Junling Wang Xiaohong Wang Pan Gu Zhigang Lei Rui Tang Chuan Wei Lei Xu Chun Wang Ying Chen Yanan Pu Xin Qi Beibei Yu Xiaojun Chen Jifeng Zhu Yalin Li Zhijie Zhang Sha Zhou Chuan Su
author_sort	Yanxiong Yu
title	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_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_sort	schistosome eggs stimulate reactive oxygen species production to enhance m2 macrophage differentiation and promote hepatic pathology in schistosomiasis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b8244d49c5c545d286106ed6d5c6c9e6
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Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis.

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