Journal
MOLECULAR IMMUNOLOGY
Volume 114, Issue -, Pages 41-48Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2019.07.012
Keywords
NLRP3; CVB3; Capsid protein; Macrophages; Viral myocarditis
Categories
Funding
- National Natural Science Foundation of China [31370894, 31470880, 31770962, 31170878, 31670898]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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Viral myocarditis, mainly caused by enteroviruses specially coxsackievirus B3 (CVB3) infection, is a common clinical cardiovascular disease and characterized by cardiac massive inflammation. Our previous study showed that CVB3-induced myocardial NLRP3 contributed to the development of viral myocarditis. In this study, we found that beside of being up-regulated in myocardiocytes, NLPR3 was also obviously increased in the cardiac infiltrating macrophages. While whether this accumulated NLRP3 influences, macrophage inflammatory responses remains unknown. By adoptive transfer assays, we found that mice receiving NLRP3 up-regulated macrophages showed much more abundant cardiac IL-1 beta production and more severe myocardial inflammation, while those receiving NLRP3 down-regulated macrophages showed much less IL-1 beta production and milder myocarditis, indicating that NLRP3 up-regulated macrophages played a pathological role in CVB3-induced myocarditis. In addition, we further found that it was CVB3 capsid proteins VP1 (predominant) and VP2, but not viral RNAs, robustly triggered macrophage NLRP3 up-regulation and activation. Our study demonstrated macrophage NLRP3 inflammasome could be efficiently be activated by CVB3 capsid proteins, and contributed to the pathogenesis of viral myocarditis. It might provide some clues to the development of new therapeutic strategies based on macrophage NLRP3 modulation.
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