Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota
| Autor: | Eugene Rudensky, Ruliang Xu, Frank Yeung, Elisabeth Kernbauer, Amanda M. Marchiando, Patricia Martin, Samantha L. Schuster, Ken Cadwell |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Receptors CCR2 Immunology Autophagy-Related Proteins Cellular homeostasis Biology Gut flora Applied Microbiology and Biotechnology Microbiology Article Monocytes Mice 03 medical and health sciences Interferon Autophagy Genetics Citrobacter rodentium medicine Animals Intestinal Mucosa Receptor Adaptor Proteins Signal Transducing Mice Knockout Enterobacteriaceae Infections Membrane Proteins Signal transducing adaptor protein Cell Biology biology.organism_classification Immunity Innate Gastrointestinal Microbiome 3. Good health Cell biology 030104 developmental biology Interferon Type I Mutation Signal transduction Carrier Proteins Signal Transduction medicine.drug |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | As a conserved pathway that lies at the intersection between host defense and cellular homeostasis, autophagy serves as a rheostat for immune reactions. In particular, autophagy suppresses excess type I interferon (IFN-I) production in response to viral nucleic acids. It is unknown how this function of autophagy relates to the intestinal barrier where host-microbe interactions are pervasive and perpetual. Here, we demonstrate that mice deficient in autophagy proteins are protected from the intestinal bacterial pathogen Citrobacter rodentium in a manner dependent on IFN-I signaling and nucleic acid sensing pathways. Enhanced IFN-stimulated gene (ISG) expression in intestinal tissue of autophagy-deficient mice in the absence of infection was mediated by the gut microbiota. Additionally, monocytes infiltrating into the autophagy-deficient intestinal microenvironment displayed an enhanced inflammatory profile and were necessary for protection against C. rodentium. Finally, we demonstrate that the microbiota-dependent IFN-I production that occurs in the autophagy-deficient host also protects against chemical injury of the intestine. Thus, autophagy proteins prevent a spontaneous IFN-I response to microbiota that is beneficial in the presence of infectious and non-infectious intestinal hazards. These results identify a role for autophagy proteins in controlling the magnitude of IFN-I signaling at the intestinal barrier. |
| Databáze: | OpenAIRE |
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