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Nat Microbiol. 2018 May;3(5):611-621. doi: 10.1038/s41564-018-0138-2. Epub 2018 Apr 9.

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

Author information

1
Howard Hughes Medical Institute, New Haven, CT, USA.
2
Department of Immunobiology, Yale University, New Haven, CT, USA.
3
New England Discovery Partners, Branford, CT, USA.
4
Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA.
5
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
6
Howard Hughes Medical Institute, New Haven, CT, USA. akiko.iwasaki@yale.edu.
7
Department of Immunobiology, Yale University, New Haven, CT, USA. akiko.iwasaki@yale.edu.

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.

Comment in

PMID:
29632368
PMCID:
PMC5918160
DOI:
10.1038/s41564-018-0138-2
[Indexed for MEDLINE]
Free PMC Article

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