小柯机器人

肠道菌群可抑制α病毒的感染和传播
2020-07-16 17:53
来源：小柯机器人

美国华盛顿大学医学院的Michael S. Diamond课题组发现，肠道微生物组通过胆汁酸I型干扰素信号轴限制α病毒的感染和传播。这一研究成果于2020年7月14日在线发表在《细胞》上。

研究人员发现，在无菌细菌小鼠或肠道菌群耗竭（通过口服抗生素处理）的常规饲养小鼠中，病毒接种后1天之内会发生更严重的基孔肯雅热病毒（CHIKV）感染和传播。微生物组的变化会改变浆细胞样树突状细胞（pDC）中的TLR7-MyD88信号传导，并减弱I型干扰素（IFN）的全身产生。因此，循环中的单核细胞表达较少的IFN刺激基因，并更容易被CHIKV感染。
 
用单个菌种梭状芽孢杆菌或其产生的代谢物（次级胆汁酸脱氧胆酸）能够恢复pDC和MyD88依赖性的I型IFN反应，从而限制全身性CHIKV感染以及其在媒介（蚊子）间的传播。因此，共生肠道细菌在感染后数小时内通过胆汁酸-pDC-IFN信号轴调节抗病毒免疫和循环α病毒水平，从而影响病毒血症、传播和潜在传播。
 
据介绍，CHIKV是一种新兴的α病毒，已感染了数百万人。但是，影响疾病结果的因素仍然知之甚少。
 
附：英文原文

Title: The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis

Author: Emma S. Winkler, Swathi Shrihari, Barry L. Hykes, Scott A. Handley, Prabhakar S. Andhey, Yan-Jang S. Huang, Amanda Swain, Lindsay Droit, Kranthi K. Chebrolu, Matthias Mack, Dana L. Vanlandingham, Larissa B. Thackray, Marina Cella, Marco Colonna, Maxim N. Artyomov, Thaddeus S. Stappenbeck, Michael S. Diamond

Issue&Volume: 2020-07-14

Abstract: Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.

DOI: 10.1016/j.cell.2020.06.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30806-0

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85
官方网址：https://www.cell.com/
投稿链接：https://www.editorialmanager.com/cell/default.aspx

本期文章：《细胞》：Online/在线发表

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