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
  • 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. [email protected].
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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