2. Academic Validation
  3. The microbial metabolite desaminotyrosine protects from influenza through type I interferon

The microbial metabolite desaminotyrosine protects from influenza through type I interferon

  • Science. 2017 Aug 4;357(6350):498-502. doi: 10.1126/science.aam5336.
Ashley L Steed 1 2,  George P Christophi 3 2,  Gerard E Kaiko 2,  Lulu Sun 2,  Victoria M Goodwin 1 2,  Umang Jain 2,  Ekaterina Esaulova 2 4,  Maxim N Artyomov 2,  David J Morales 3 2,  Michael J Holtzman 3,  Adrianus C M Boon 3 2 5,  Deborah J Lenschow 3 2,  Thaddeus S Stappenbeck 6
Affiliations

Affiliations

  • 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.
PMID: 28774928 DOI: 10.1126/science.aam5336
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.

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