Nature子刊:氨基糖苷类抗生素的抗病毒机制

Nature Microbiology

4/9/18Article

N/A

影响因子

原标题:氨基糖苷类抗生素的局部使用以不依赖菌群的方式增强宿主对病毒感染的抵抗力

① 在局部粘膜(如阴道和鼻粘膜)预防性使用氨基糖苷类抗生素,可增强小鼠对多种病毒感染的抵抗力,包括单纯疱疹病毒,甲型流感病毒和寨卡病毒;② 氨基糖苷类抗生素可减少原代人细胞中的病毒复制,其抗病毒活性不依赖于菌群,在无菌小鼠中同样有效;③ 机制是:经Toll样受体3(TLR3)和下游信号传导通路,显著上调干扰素刺激基因(ISG)的转录;④ 特异表达TLR3的XCR1+树突细胞在氨基糖苷类抗生素处理后被募集到粘膜,是诱导ISG表达所必需的。

氨基糖苷类抗生素 抗病毒 干扰素刺激基因(ISG) XCR1+树突细胞 Toll样受体3

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Title:
Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner

DOI:
10.1038/s41564-018-0138-2

Abstract & Authors展开

Abstract:
Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. Here we identify an antiviral effect of commonly used aminoglycoside antibiotics. We show that topical mucosal application of aminoglycosides prophylactically increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota, because aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by Toll-like receptor 3, and required Toll/interleukin-1-receptor-domain-containing adapter-inducing interferon-β signalling adaptor, and Interferon regulatory factors 3 and 7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express Toll-like receptor 3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistance in vivo.

All Authors:
Smita Gopinath, Myoungjoo V Kim, Tasfia Rakib, Patrick W Wong, Michael van Zandt, Natasha A Barry, Tsuneyasu Kaisho, Andrew L Goodman , Akiko Iwasaki

First Authors:
Smita Gopinath

Correspondence:
Akiko Iwasaki

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