Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou 215004, China.
Viruses. 2023 Apr 28;15(5):1078. doi: 10.3390/v15051078.
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 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.
炎症小体是病原体的细胞溶质传感器。它们的激活可导致半胱天冬酶-1 介导的炎症反应的诱导和几种促炎细胞因子的释放，包括 IL-1β。病毒感染与核苷酸结合寡聚化结构域样受体家族 pyrin 结构域包含 3（NLRP3）炎症小体之间存在复杂的关系。NLRP3 炎症小体的激活对于抗病毒免疫至关重要，而过度的 NLRP3 炎症小体激活可能导致过度的炎症和病理损伤。同时，病毒已经进化出抑制炎症小体信号通路激活的策略，从而逃避免疫反应。在这项研究中，我们研究了柯萨奇病毒 B3（CVB3），一种正单链 RNA 病毒，对巨噬细胞中 NLRP3 炎症小体激活的抑制作用。LPS 刺激后，感染 CVB3 的小鼠的 IL-1β产生和小肠中的 NLRP3 水平显着降低。此外，我们发现 CVB3 感染通过抑制 NF-κB 信号通路和 ROS 产生来抑制巨噬细胞中 NLRP3 炎症小体的激活和 IL-1β 的产生。此外，CVB3 感染通过降低 IL-1β 的产生，增加了小鼠对 的易感性。总之，我们的研究揭示了一种通过抑制 LPS 诱导的巨噬细胞中 NF-κB 途径和 ROS 产生来激活 NLRP3 炎症小体的新机制。我们的研究结果可能为 CVB3 感染的抗病毒治疗和药物开发提供新的思路。
