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Science. 2017 Aug 4;357(6350):498-502. doi: 10.1126/science.aam5336.

The microbial metabolite desaminotyrosine protects from influenza through type I interferon.

Author information

1
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Computer Technologies Department, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics, Saint Petersburg 197101, Russia.
5
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. stappenb@pathology.wustl.edu.

Abstract

The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.

Comment in

PMID:
28774928
PMCID:
PMC5753406
DOI:
10.1126/science.aam5336
[Indexed for MEDLINE]
Free PMC Article

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