Centre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308, 69365 Lyon Cedex 07, France.
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10404-10409. doi: 10.1073/pnas.1722372115. Epub 2018 Sep 24.
Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.
肠道微生物群（称为“生态失调”）的显著变化在过敏疾病的发展中起关键作用，但潜在机制尚不清楚。对小鼠迟发型超敏反应（DTH）的研究有助于我们了解人类过敏性接触性皮炎的病理生理学。在这里，我们报告了 RIG-I 样受体接头线粒体抗病毒信号（MAVS）通过调节肠道细菌生态对 DTH 的负调节作用。共笼和粪便移植实验表明，小鼠的生态失调微生物群赋予了一种过敏性表型，可传播给野生型小鼠。DTH 致敏与肠道通透性增加和肠道细菌易位到淋巴器官同时发生，从而加重了 DTH 的严重程度。总之，我们揭示了 RIG-I 样信号对肠道微生物群的意外影响，这对过敏性皮肤疾病的结果有影响。这些数据主要表明，操纵肠道微生物群可能有助于开发治疗人类过敏性皮肤疾病的治疗策略。
