Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, India.
Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA, USA.
Cell Death Dis. 2022 Jun 2;13(6):520. doi: 10.1038/s41419-022-04954-y.
Intracellular and cell surface pattern-recognition receptors (PRRs) are an essential part of innate immune recognition and host defense. Here, we have compared the innate immune responses between humans and bats to identify a novel membrane-associated protein, Rnd1, which defends against viral and bacterial infection in an interferon-independent manner. Rnd1 belongs to the Rho GTPase family, but unlike other small GTPase members, it is constitutively active. We show that Rnd1 is induced by pro-inflammatory cytokines during viral and bacterial infections and provides protection against these pathogens through two distinct mechanisms. Rnd1 counteracts intracellular calcium fluctuations by inhibiting RhoA activation, thereby inhibiting virus internalisation. On the other hand, Rnd1 also facilitates pro-inflammatory cytokines IL-6 and TNF-α through Plxnb1, which are highly effective against intracellular bacterial infections. These data provide a novel Rnd1-mediated innate defense against viral and bacterial infections.
细胞内和细胞表面模式识别受体（PRRs）是先天免疫识别和宿主防御的重要组成部分。在这里，我们比较了人类和蝙蝠的先天免疫反应，以鉴定一种新型的膜相关蛋白 Rnd1，它以干扰素非依赖的方式抵抗病毒和细菌感染。Rnd1 属于 Rho GTPase 家族，但与其他小 GTPase 成员不同，它是组成性激活的。我们表明，Rnd1 在病毒和细菌感染期间由促炎细胞因子诱导，并通过两种不同的机制提供针对这些病原体的保护。Rnd1 通过抑制 RhoA 激活来抵抗细胞内钙波动，从而抑制病毒内化。另一方面，Rnd1 还通过 Plxnb1 促进促炎细胞因子 IL-6 和 TNF-α 的产生，这对细胞内细菌感染非常有效。这些数据提供了一种新的 Rnd1 介导的针对病毒和细菌感染的先天防御。
