TY - JOUR
T1 - The microbial metabolite desaminotyrosine protects from influenza through type I interferon
AU - Steed, Ashley L.
AU - Christophi, George P.
AU - Kaiko, Gerard E.
AU - Sun, Lulu
AU - Goodwin, Victoria M.
AU - Jain, Umang
AU - Esaulova, Ekaterina
AU - Artyomov, Maxim N.
AU - Morales, David J.
AU - Holtzman, Michael J.
AU - Boon, Adrianus C.M.
AU - Lenschow, Deborah J.
AU - Stappenbeck, Thaddeus S.
N1 - Publisher Copyright:
© 2017, American Association for the Advancement of Science. All rights reserved.
PY - 2017/8/4
Y1 - 2017/8/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85026755340&partnerID=8YFLogxK
U2 - 10.1126/science.aam5336
DO - 10.1126/science.aam5336
M3 - Article
C2 - 28774928
AN - SCOPUS:85026755340
SN - 0036-8075
VL - 357
SP - 498
EP - 502
JO - Science
JF - Science
IS - 6350
ER -