Winkler, Emma S. and Shrihari, Swathi and Hykes, Barry L. and Handley, Scott A. and Andhey, Prabhakar S. and Huang, Yan-Jang S. and Swain, Amanda and Droit, Lindsay and Chebrolu, Kranthi K. and Mack, Matthias and Vanlandingham, Dana L. and Thackray, Larissa B. and Cella, Marina and Colonna, Marco and Artyomov, Maxim N. and Stappenbeck, Thaddeus S. and Diamond, Michael S. (2020) The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis. CELL, 182 (4). 901-+. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)Abstract
Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHIKUNGUNYA VIRUS-INFECTION; FARNESOID X RECEPTOR; SALT BIOTRANSFORMATIONS; MONOCLONAL-ANTIBODY; INNATE IMMUNITY; MICE; CELLS; REPLICATION; INTERFERONS; INFLUENZA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2021 07:21 |
| Last Modified: | 16 Mar 2021 07:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43995 |
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