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

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...

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Detalles Bibliográficos
Autores principales: Martin, Patricia K., Marchiando, Amanda, Xu, Ruliang, Rudensky, Eugene, Yeung, Frank, Schuster, Samantha L., Kernbauer, Elisabeth, Cadwell, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179362/
https://www.ncbi.nlm.nih.gov/pubmed/30202015
http://dx.doi.org/10.1038/s41564-018-0229-0
Descripción
Sumario: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.