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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.
Steed AL1,2, Christophi GP3,2, Kaiko GE2, Sun L2, Goodwin VM1,2, Jain U2, Esaulova E2,4, Artyomov MN2, Morales DJ3,2, Holtzman MJ3, Boon ACM3,2,5, Lenschow DJ3,2, Stappenbeck TS6.
Author information
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.
Copyright ? 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID: 28774928 DOI: 10.1126/science.aam5336
The microbial metabolite desaminotyrosine protects from influenza through type I interferon.
Steed AL1,2, Christophi GP3,2, Kaiko GE2, Sun L2, Goodwin VM1,2, Jain U2, Esaulova E2,4, Artyomov MN2, Morales DJ3,2, Holtzman MJ3, Boon ACM3,2,5, Lenschow DJ3,2, Stappenbeck TS6.
Author information
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.
Copyright ? 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID: 28774928 DOI: 10.1126/science.aam5336