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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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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 |
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author | Martin, Patricia K. Marchiando, Amanda Xu, Ruliang Rudensky, Eugene Yeung, Frank Schuster, Samantha L. Kernbauer, Elisabeth Cadwell, Ken |
author_facet | Martin, Patricia K. Marchiando, Amanda Xu, Ruliang Rudensky, Eugene Yeung, Frank Schuster, Samantha L. Kernbauer, Elisabeth Cadwell, Ken |
author_sort | Martin, Patricia K. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6179362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-61793622019-03-10 Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota Martin, Patricia K. Marchiando, Amanda Xu, Ruliang Rudensky, Eugene Yeung, Frank Schuster, Samantha L. Kernbauer, Elisabeth Cadwell, Ken Nat Microbiol Article 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. 2018-09-10 2018-10 /pmc/articles/PMC6179362/ /pubmed/30202015 http://dx.doi.org/10.1038/s41564-018-0229-0 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Martin, Patricia K. Marchiando, Amanda Xu, Ruliang Rudensky, Eugene Yeung, Frank Schuster, Samantha L. Kernbauer, Elisabeth Cadwell, Ken Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota |
title | Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota |
title_full | Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota |
title_fullStr | Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota |
title_full_unstemmed | Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota |
title_short | Autophagy proteins suppress protective type I interferon signaling in response to the murine gut microbiota |
title_sort | autophagy proteins suppress protective type i interferon signaling in response to the murine gut microbiota |
topic | Article |
url | 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 |
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