Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and induces an immune response that prevents experimental colitis
Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and induces an immune response that prevents experimental colitis
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DOI：
10.1073/pnas.1107114108
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发表时间：
2011-10-18
影响因子：
11.1
通讯作者：
Chen, Zhijian J.
中科院分区：
文献类型：
--
作者：
Li, Xiao-Dong;Chiu, Yu-Hsin;Chen, Zhijian J.
RIG-I样受体(RLRs)通过招募线粒体适配器蛋白MAV(也称为IPS1、VISA或CADIF)来激活宿主对病毒感染的先天免疫反应。在这里，我们表明MAV在维持肠道内环境稳定方面也起着关键作用。我们发现，在实验性结肠炎模型中，MAVS基因敲除小鼠比WT动物表现出更严重的死亡率和发病率。骨髓移植实验表明，非造血源细胞中的MAV在预防结肠炎中起主导作用。重要的是，来自肠道共生细菌的RNA物种激活RIG-I-MAVS途径，诱导多种细胞因子和抗菌肽的产生，包括干扰素-β和RegIII-γ。这些结果揭示了MAV在监测肠道共生菌和维持组织内稳态方面以前未被探索的作用。
RIG-I-like receptors (RLRs) activate host innate immune responses against virus infection through recruiting the mitochondrial adaptor protein MAVS (also known as IPS1, VISA, or CARDIF). Here we show that MAVS also plays a pivotal role in maintaining intestinal homeostasis. We found that MAVS knockout mice developed more severe mortality and morbidity than WT animals in an experimental model of colitis. Bone marrow transplantation experiments revealed that MAVS in cells of nonhematopoietic origin plays a dominant role in the protection against colitis. Importantly, RNA species derived from intestinal commensal bacteria activate the RIG-I-MAVS pathway to induce the production of multiple cytokines and antimicrobial peptides, including IFN-beta and RegIII gamma. These results unveil a previously unexplored role of MAVS in monitoring intestinal commensal bacteria and maintaining tissue homeostasis.