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 - Funding Information:
This work was supported by the Pediatric Scientist Development Program and funded by the National Institute of Child Health and Human Development, NIH 5K12HD000850-30 (A.L.S.), T32 DK007130-43 (G.P.C.), NIAID U19-AI070412 (MJH and TS), R01-AI111605 (MJH) and the Crohn’s and Colitis Foundation/Helmsley Charitable Trust. Additionally, we thank D. Kreamalmeyer for expertise in animal care and the Proteomics and Mass Spectrometry Facility at the Danforth Plant Science Center. All data to understand and assess the conclusions of this research are available in the main text and supplementary materials. RNA sequencing data are available via the following repository: ArrayExpress website, accession no. E-MTAB-5337. T.S.S., A.L.S., G.P.C., and G.E.K. are inventors on patent application no. 62413241 submitted by Washington University that covers the use of desaminotyrosine to enhance type I interferon stimulation.
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 -