Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.

蝙蝠的特殊之处在于它们具有长寿和宿主许多新兴病毒的能力。我们之前的研究表明，蝙蝠改变了炎症小体，而炎症小体是衰老和感染的关键因素。然而，炎症体信号传导在对抗炎症性疾病中的作用仍然知之甚少。在这里，我们报告蝙蝠 ASC2 是炎症小体的有效负调节因子。Bat ASC2 在 mRNA 和蛋白质水平上均高度表达，并且能够高效抑制人类和小鼠炎症小体。小鼠中蝙蝠 ASC2 的转基因表达降低了痛风晶体和 ASC 颗粒诱导的腹膜炎的严重程度。蝙蝠 ASC2 还可以抑制多种病毒引起的炎症并降低死亡率甲型流感病毒感染。重要的是，它还抑制了 SARS-CoV-2 免疫复合物诱导的炎症小体激活。确定了蝙蝠 ASC2 功能获得的四个关键残基。我们的结果表明，蝙蝠 ASC2 是炎症小体的重要负调节因子，具有治疗炎症疾病的潜力。