Macrophage NLRP3 inflammasome activated by CVB3 capsid proteins contributes to the development of viral myocarditis
Macrophage NLRP3 inflammasome activated by CVB3 capsid proteins contributes to the development of viral myocarditis
复制标题
CVB3衣壳蛋白激活的巨噬细胞NLRP3炎性体有助于病毒性心肌炎的发生
DOI：
10.1016/j.molimm.2019.07.012
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发表时间：
2019-10-01
影响因子：
3.6
通讯作者：
Xiong, Sidong
中科院分区：
文献类型：
--
作者：
Bao, Jingyin;Sun, Tianle;Xiong, Sidong
病毒性心肌炎是临床上常见的心血管疾病，主要由肠道病毒特别是柯萨奇病毒B3（CVB 3）感染引起，以心脏大面积炎症为特征。我们的前期研究表明，CVB 3诱导的心肌NLRP 3参与了病毒性心肌炎的发生。在本研究中，我们发现NLPR 3除了在心肌细胞中表达上调外，在心肌浸润的巨噬细胞中也明显上调。虽然这种累积的NLRP 3是否影响巨噬细胞的炎症反应仍然是未知的。通过过继转移试验，我们发现接受NLRP 3上调的巨噬细胞显示出更丰富的心脏IL-1 β产生和更严重的心肌炎症，而接受NLRP 3下调的巨噬细胞显示出更少的IL-1 β产生和更轻的心肌炎，表明NLRP 3上调的巨噬细胞在CVB 3诱导的心肌炎中起病理作用。此外，我们进一步发现，它是CVB 3衣壳蛋白VP 1（主要）和VP 2，而不是病毒RNA，强烈触发巨噬细胞NLRP 3的上调和激活。我们的研究表明，巨噬细胞NLRP 3炎性体可以被CVB 3衣壳蛋白有效激活，并参与病毒性心肌炎的发病机制。这可能为基于巨噬细胞NLRP 3调节的新治疗策略的开发提供一些线索。
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.