The microbial metabolite desaminotyrosine protects from influenza through type I interferon
Eat more plants for influenza resilience
Antibiotic treatment worsens influenza in mice, possibly because the concomitant loss of the microbiota interrupts the production of bioactive metabolites. Steed et al. found that a microbial product, desaminotyrosine (DAT), produced by an obligate clostridial anaerobe from the digestion of plant flavonoids, is beneficial during influenza. DAT enters the bloodstream and triggers type I interferon signaling, which then augments antiviral responses by phagocytic cells. Without DAT, influenza virus causes inflammation and severe disease.
Science, this issue p. 498
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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Supplementary Material
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Materials and Methods
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Information & Authors
Information
Published In
Science
Volume 357 • Issue 6350 • 4 August 2017
Pages: 498 - 502
History
Received: 5 December 2016
Revision received: 28 April 2017
Accepted: 15 June 2017
Copyright
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Crohn’s Colitis: award312855
Why some flu strains become deadly?
The current flu in Hong Kong claimed hundreds of lives, with a mortality rate of nearly 2%. The major Influenza A strain circulating in Hong Kong is characterized by a N121K amino acid substitution (1). Lysine is a positively charged basic amino acid capable of binding anions. Anions such as Cl- could be deadly to cells either acting alone or in the form of strong acids. Overrepresentation of essential amino acids is a hallmark of numerous virulent viruses (2-5). As lysine is an essential amino acid, it was previously proposed that a starch staple or plant-based diet could be beneficial against viral infections (5-6).
Yunfan Shi, 1,4 Ying Zhang, 2,4 Ling Wen, 3 Qiuyun Liu 1,*
1. Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Biomedical Center, Lab of Microbial Metabolic Engineering and Synthetic Biology, State Key Laboratory of Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
2. Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China.
3. Twelfth People's Hospital, Tianhe, Guangzhou 510620, China.
4. Equal contributions.
*Correspondence author.
E-mail address: [email protected] (Q. Liu)
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ACKNOWLEDGMENT
Manuscript editing by Ms. Yan Shi, and support from Guangzhou Science and Technology Program (General project 2018) and NNSF are appreciated.