Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ
Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ
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DOI：
10.1038/s41564-019-0416-7
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发表时间：
2019-07-01
影响因子：
28.3
通讯作者：
Baldridge, Megan T.
中科院分区：
文献类型：
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作者：
Ingle, Harshad;Lee, Sanghyun;Baldridge, Megan T.
共生微生物深刻影响宿主对肠道病毒感染的免疫力（1）。我们已经证明，细菌微生物群和宿主抗病毒细胞因子干扰素-λ（IFN-λ）决定了肠道中鼠诺如病毒的持久性（2，3）。然而，病毒组在调节肠道感染中的作用仍然未被探索。在这里，我们报告说，鼠星状病毒可以补充原发性免疫缺陷，以防止鼠诺如病毒和轮状病毒感染。免疫功能低下的小鼠品系之间的保护感染是水平转移的共同住房和粪便移植。此外，对肠道病原体的保护与肠道中存在特定的鼠星状病毒株相对应，这种免疫缺陷的互补需要肠道上皮细胞中的IFN-λ信号传导。我们的研究表明，病毒组的元素可以保护免疫缺陷宿主免受肠道病原体的侵害。
Commensal microbes profoundly impact host immunity to enteric viral infections(1). We have shown that the bacterial microbiota and host antiviral cytokine interferon-lambda (IFN-lambda) determine the persistence of murine norovirus in the gut(2,3). However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-lambda signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.