The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon
The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon
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DOI：
10.1038/s41564-019-0602-7
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发表时间：
2020-01-01
影响因子：
28.3
通讯作者：
Karst, Stephanie M.
中科院分区：
文献类型：
--
作者：
Grau, Katrina R.;Zhu, Shu;Karst, Stephanie M.
已经积累的证据表明，肠道微生物群增强哺乳动物肠道病毒感染（1）。例如，我们和其他人以前报道过肠道细菌刺激急性和持续的鼠诺如病毒感染（2-4）。然而，与这些结果明显矛盾的是，小鼠诺如病毒感染的毒力不受抗生素治疗的影响。这促使我们对微生物耗竭小鼠中的小鼠诺如病毒感染进行详细研究，揭示了一个更复杂的画面，其中肠道细菌抑制近端小肠的病毒感染，同时刺激肠道远端区域的感染。因此，肠道细菌可以调节病毒沿着肠道的区域化。我们进一步表明，诺如病毒感染的近端肠道细菌依赖性抑制的机制涉及胆汁酸引发的III型干扰素。最后，微生物群对诺如病毒感染的区域效应可能是由调节III型干扰素应答的关键胆汁酸受体的不同区域表达谱引起的。总的来说，这些发现揭示了肠道微生物群对宿主代谢物的生物转化直接和区域性地影响致病性肠道病毒的感染。
Evidence has accumulated to demonstrate that the intestinal microbiota enhances mammalian enteric virus infections(1). For example, we and others previously reported that commensal bacteria stimulate acute and persistent murine norovirus infections(2-4). However, in apparent contradiction of these results, the virulence of murine norovirus infection was unaffected by antibiotic treatment. This prompted us to perform a detailed investigation of murine norovirus infection in microbially deplete mice, revealing a more complex picture in which commensal bacteria inhibit viral infection of the proximal small intestine while simultaneously stimulating the infection of distal regions of the gut. Thus, commensal bacteria can regulate viral regionalization along the intestinal tract. We further show that the mechanism underlying bacteria-dependent inhibition of norovirus infection in the proximal gut involves bile acid priming of type III interferon. Finally, the regional effects of the microbiota on norovirus infection may result from distinct regional expression profiles of key bile acid receptors that regulate the type III interferon response. Overall, these findings reveal that the biotransformation of host metabolites by the intestinal microbiota directly and regionally impacts infection by a pathogenic enteric virus.