Macrophage NLRP3 inflammasome activated by CVB3 capsid proteins contributes to the development of viral myocarditis

• Published in: Molecular immunology Vol. 114; pp. 41 - 48
• Main Authors: Bao, Jingyin, Sun, Tianle, Yue, Yan, Xiong, Sidong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2019
• Subjects: Adoptive Transfer - methods; Animals; Capsid protein; Capsid Proteins - immunology; Cell Line; Cell Line, Tumor; Coxsackievirus Infections - immunology; CVB3; Down-Regulation - immunology; Enterovirus - immunology; Heart - virology; HeLa Cells; Humans; Inflammasomes - immunology; Inflammation - immunology; Macrophages; Macrophages - immunology; Macrophages - virology; Male; Mice; Mice, Inbred BALB C; Myocarditis - immunology; Myocarditis - virology; Myocardium - immunology; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLRP3; RAW 264.7 Cells; Up-Regulation - immunology; Viral myocarditis; Virus Diseases - immunology; Virus Diseases - virology; NLRP3; CVB3; Capsid protein; Macrophages; Viral myocarditis
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2019.07.012

•NLRLP3 inflammasome was activated in the cardiac macrophages of CVB3-infected mice.•NLRP3 activacted macrophages contributed greatly to the pathogenesis of myocarditis.•CVB3 capsid proteins VP1 and VP2 triggered macrophage NLRP3 inflammasome activation.
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-1β production and more severe myocardial inflammation, while those receiving NLRP3 down-regulated macrophages showed much less IL-1β 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.