Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota.

Autor: Martin PK; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA.; Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY, USA., Marchiando A; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA., Xu R; Department of Pathology, New York University School of Medicine, New York, NY, USA., Rudensky E; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA.; Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY, USA., Yeung F; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA.; Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY, USA., Schuster SL; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA., Kernbauer E; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA., Cadwell K; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA. ken.cadwell@med.nyu.edu.; Department of Microbiology, New York University School of Medicine, New York, NY, USA. ken.cadwell@med.nyu.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2018 Oct; Vol. 3 (10), pp. 1131-1141. Date of Electronic Publication: 2018 Sep 10.
DOI: 10.1038/s41564-018-0229-0
Abstrakt: 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.
Databáze: MEDLINE
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