Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Cell Rep. 2023 Oct 31;42(10):113261. doi: 10.1016/j.celrep.2023.113261. Epub 2023 Oct 16.
Cyclic di-guanosine monophosphate (c-di-GMP) is a unique bacterial second messenger but is hijacked by host cells during bacterial infection as a pathogen-associated molecular pattern (PAMP) to trigger STING-dependent immune responses. Here, we show that upon infection, VopY, an effector of Vibrio parahaemolyticus, is injected into host cells by type III secretion system 2 (T3SS2), a secretion system unique to its pathogenic strains and indispensable for enterotoxicity. VopY is an EAL-domain-containing phosphodiesterase and is capable of hydrolyzing c-di-GMP. VopY expression in host cells prevents the activation of STING and STING-dependent downstream signaling triggered by c-di-GMP and, consequently, suppresses type I interferon immune responses. The presence of VopY in V. parahaemolyticus enables it to cause both T3SS2-dependent enterotoxicity and cytotoxicity. These findings uncover the destruction of self-derived PAMPs by injecting specific effectors to suppress PAMP-triggered immune responses as a unique strategy for bacterial pathogens to subvert immunity and cause disease.
环二鸟苷酸（cyclic di-GMP）是一种独特的细菌第二信使，但在细菌感染过程中被宿主细胞劫持为病原体相关分子模式（PAMP），以触发 STING 依赖性免疫反应。在这里，我们表明，在感染过程中，副溶血弧菌的效应子 VopY 通过 III 型分泌系统 2（T3SS2）注入宿主细胞，III 型分泌系统 2 是其致病株所特有的分泌系统，对肠毒性是不可或缺的。VopY 是一个 EAL 结构域包含的磷酸二酯酶，能够水解 c-di-GMP。宿主细胞中 VopY 的表达可防止 c-di-GMP 激活 STING 和 STING 依赖性下游信号，并因此抑制 I 型干扰素免疫反应。副溶血弧菌中 VopY 的存在使其能够引起 T3SS2 依赖性肠毒性和细胞毒性。这些发现揭示了细菌病原体通过注射特异性效应子来破坏自身衍生的 PAMP，以抑制 PAMP 触发的免疫反应，这是一种独特的策略，以颠覆宿主的免疫并导致疾病。
