期刊
NATURE MICROBIOLOGY
卷 3, 期 10, 页码 1131-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41564-018-0229-0
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资金
- US National Institute of Health (NIH) [R01 HL123340, R01 DK093668, R01 DK103788, R01 AI121244, F31 DK111139, T32 AI100853]
- Howard Hughes Medical Institute
- Merieux Institute
- Rainin Foundation Innovator Award
- Stony Wold-Herbert Fund
- Crohn's & Colitis Foundation Research Fellowship Award
As a conserved pathway that lies at the intersection between host defence 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 signalling and nucleic acid sensing pathways. Enhanced IFN-stimulated gene 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 signalling at the intestinal barrier.
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