In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 8 ( 2021-8-16), p. e0009696-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009696
DOI:
10.1371/journal.pntd.0009696.g001
DOI:
10.1371/journal.pntd.0009696.g002
DOI:
10.1371/journal.pntd.0009696.g003
DOI:
10.1371/journal.pntd.0009696.g004
DOI:
10.1371/journal.pntd.0009696.g005
DOI:
10.1371/journal.pntd.0009696.g006
DOI:
10.1371/journal.pntd.0009696.s001
DOI:
10.1371/journal.pntd.0009696.r001
DOI:
10.1371/journal.pntd.0009696.r002
DOI:
10.1371/journal.pntd.0009696.r003
DOI:
10.1371/journal.pntd.0009696.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
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