title: IL-33 enhances macrophage M2 polarization and protects mice from CVB3-induced viral myocarditis.
abstract: Viral myocarditis is the inflammation caused by myocardial virus infection, and the coxsackievirus group B3 virus (CVB3) is the most common pathogen. An efficient therapeutic agent against viral myocarditis is currently unavailable. IL-33, a new member of the IL-1 cytokine superfamily, exhibits potential immunotherapeutic effect against inflammatory and autoimmune diseases. However, the functional role of IL-33 in viral myocarditis has not been investigated. To examine the therapeutic role of IL-33 in viral myocarditis, an IL-33 overexpression plasmid (pDisplay-IL-33) and IL-33 knockdown plasmid (pLL3.7-IL-33) were packaged with polyethylenimine and delivered intravenously at the orbital area of BALB/c male mice after CVB3 infection. Then, myocarditis severity was assessed 7days after infection. Results showed that IL-33 up-regulation significantly alleviated the severity of viral myocarditis with an increased cardiac contractive function and survival rate. Mechanistic studies demonstrated that IL-33 can stimulate ST2L+F4/80+macrophages and ST2L+CD4+T cells in cardiac tissue to express IL-4, which is a potent inducer for macrophage M2 polarization. Mice with adoptive transfer of M2 macrophages exhibited less cardiac inflammation and attenuated myocarditis, suggesting the protective role of M2 macrophage in viral myocarditis. Additionally, IL-4 neutralization abolished the IL-33-mediated cardiac functional improvement in myocarditis mice. Collectively, our findings provide a novel therapeutic role for IL-33 in CVB3-induced myocarditis.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, PR China. Electronic address: chunshengdong@suda.edu.cn.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, PR China. Electronic address: sdxiongfd@126.com.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers; D003384:Coxsackievirus Infections / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004452:Echocardiography; D029822:Enterovirus B, Human; D018836:Inflammation Mediators / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D010641:Phenotype
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D000067596:Interleukin-33
keywords: Coxsackievirus; IL-33; Macrophage polarization; Viral myocarditis