Affiliation:
1. Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China
2. Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou 215004, China
Abstract
Inflammasomes are cytosolic sensors of pathogens. Their activation can lead to the induction of caspase-1-mediated inflammatory responses and the release of several proinflammatory cytokines, including IL-1β. There is a complex relationship between viral infection and the nucleotide-binding oligomerization domain-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome. The activation of the NLRP3 inflammasome is essential for antiviral immunity, while excessive NLRP3 inflammasome activation may lead to excessive inflammation and pathological damage. Meanwhile, viruses have evolved strategies to suppress the activation of inflammasome signaling pathways, thus escaping immune responses. In this study, we investigated the inhibitory effect of coxsackievirus B3 (CVB3), a positive single-strand RNA virus, on the activation of the NLRP3 inflammasome in macrophages. CVB3-infected mice had significantly lower production of IL-1β and a lower level of NLRP3 in the small intestine after LPS stimulation. Furthermore, we found that CVB3 infection inhibited NLRP3 inflammasome activation and IL-1β production in macrophages by suppressing the NF-κB signaling pathway and ROS production. Additionally, CVB3 infection increased the susceptibility of mice to Escherichia coli infection by decreasing IL-1β production. Collectively, our study revealed a novel mechanism of NLRP3 inflammasome activation by suppressing the NF-κB pathway and ROS production in LPS-induced macrophages. Our findings may provide new ideas for antiviral treatment and drug development for CVB3 infection.
Funder
Chinese National Natural Science Foundation
the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Natural Science Foundation of Universities in Anhui Province
the Natural Science Foundation BoXi Program funded by the First Affiliated Hospital of Soochow University
Priority Academic Program Development of Jiangsu Higher Education Institutions
Subject
Virology,Infectious Diseases
Cited by
2 articles.
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