The microbial metabolite desaminotyrosine protects from influenza through type I interferon

Ashley L. Steed, George P. Christophi, Gerard E. Kaiko, Lulu Sun,Victoria M. Goodwin,Umang Jain, Ekaterina Esaulova, Maxim N. Artyomov, David J. Morales, Michael J. Holtzman, Adrianus C. M. Boon, Deborah J. Lenschow, Thaddeus S. Stappenbeck

Science 357 (6350), 498-502.

Speaker：Hung-Chuan Chang            Time：14：00~15：00, Nov.29, 2017

Commentator：Dr. Li-Chiu Wang         Place：Room 601

Abstract：

           Previous studies have confirmed that microbiota can regulate the host immune response to influenza virus infection, but the main mechanism is unclear. In this study, the authors hypothesized that metabolite of the microbiota can induced type I interferon activation to protect influenza virus infection. This hypothesis are supported by influenza analysis in a gain-of-function genetic mouse model, immunity- related guanosine triphosphatase family Mmember 1 (Irgm1) gene knockout mice assessment performed of type I interferon prior to influenza infection and lead to an appropriate and systemic type I interferon response. Also, the data showed that the microbial-related metabolite, deaminotyrosine (DAT), enhance type I interferon signaling to prevent influenza virus infection and reducing damage of airway epithelial cells. In this experiment, Clostridium orbiscindens, a specific human intestinal microbiota produced DAT and rescued antibiotic treated influenza-infected mice. DAT protected the host by triggering a downstream factor of type I interferon receptor. These findings indicate that metabolites of the enteric microbiota have a significant effect by adjust the type I interferon to protect influenza virus infection.

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