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Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells

Stressful life events are considered a risk factor for autoimmune disorders, though the mechanisms are unclear. Here we demonstrate that chronic social stress induces virulence-associated transcriptional patterns in the murine gut microbiota. The stress-influenced microbiota increased the presence o...

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Autores principales: Werbner, Michal, Barsheshet, Yiftah, Werbner, Nir, Zigdon, Mor, Averbuch, Itamar, Ziv, Oren, Brant, Boris, Elliot, Evan, Gelberg, Shachaf, Titelbaum, Moran, Koren, Omry, Avni, Orly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517692/
https://www.ncbi.nlm.nih.gov/pubmed/31098398
http://dx.doi.org/10.1128/mSystems.00292-18
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author Werbner, Michal
Barsheshet, Yiftah
Werbner, Nir
Zigdon, Mor
Averbuch, Itamar
Ziv, Oren
Brant, Boris
Elliot, Evan
Gelberg, Shachaf
Titelbaum, Moran
Koren, Omry
Avni, Orly
author_facet Werbner, Michal
Barsheshet, Yiftah
Werbner, Nir
Zigdon, Mor
Averbuch, Itamar
Ziv, Oren
Brant, Boris
Elliot, Evan
Gelberg, Shachaf
Titelbaum, Moran
Koren, Omry
Avni, Orly
author_sort Werbner, Michal
collection PubMed
description Stressful life events are considered a risk factor for autoimmune disorders, though the mechanisms are unclear. Here we demonstrate that chronic social stress induces virulence-associated transcriptional patterns in the murine gut microbiota. The stress-influenced microbiota increased the presence of effector T helper cells in the mesenteric lymph nodes, including myelin-autoreactive cells. Inhibition of the bacterial quorum sensor QseC, which is also responsive to norepinephrine, diminished the presence of effector T helper cells and bacteria such as Acinetobacter in the mesenteric lymph nodes, without remarkably affecting the gut microbial composition. Together, our results delineate a model in which the immune reaction to stress-responsive microbiota may compromise tolerance to self and therefore may increase the risk for autoimmune diseases in susceptible individuals. IMPORTANCE How do stressful life events increase the risk for autoimmune disorders? Here we show that chronic social stress in mice promotes the expression of virulent genes in the gut microbiota and alters the microbial translocation into the mesenteric lymph nodes. Our results also suggest that the consequent immune response to the stress-affected microbiota may endanger the tolerance for self. The presence of specific translocated bacteria and the immune response in the mesenteric lymph nodes can be diminished using an inhibitor of the bacterial communication system without drastically affecting the gut microbial composition as antibiotics do.
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spelling pubmed-65176922019-05-16 Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells Werbner, Michal Barsheshet, Yiftah Werbner, Nir Zigdon, Mor Averbuch, Itamar Ziv, Oren Brant, Boris Elliot, Evan Gelberg, Shachaf Titelbaum, Moran Koren, Omry Avni, Orly mSystems Research Article Stressful life events are considered a risk factor for autoimmune disorders, though the mechanisms are unclear. Here we demonstrate that chronic social stress induces virulence-associated transcriptional patterns in the murine gut microbiota. The stress-influenced microbiota increased the presence of effector T helper cells in the mesenteric lymph nodes, including myelin-autoreactive cells. Inhibition of the bacterial quorum sensor QseC, which is also responsive to norepinephrine, diminished the presence of effector T helper cells and bacteria such as Acinetobacter in the mesenteric lymph nodes, without remarkably affecting the gut microbial composition. Together, our results delineate a model in which the immune reaction to stress-responsive microbiota may compromise tolerance to self and therefore may increase the risk for autoimmune diseases in susceptible individuals. IMPORTANCE How do stressful life events increase the risk for autoimmune disorders? Here we show that chronic social stress in mice promotes the expression of virulent genes in the gut microbiota and alters the microbial translocation into the mesenteric lymph nodes. Our results also suggest that the consequent immune response to the stress-affected microbiota may endanger the tolerance for self. The presence of specific translocated bacteria and the immune response in the mesenteric lymph nodes can be diminished using an inhibitor of the bacterial communication system without drastically affecting the gut microbial composition as antibiotics do. American Society for Microbiology 2019-05-14 /pmc/articles/PMC6517692/ /pubmed/31098398 http://dx.doi.org/10.1128/mSystems.00292-18 Text en Copyright © 2019 Werbner et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Werbner, Michal
Barsheshet, Yiftah
Werbner, Nir
Zigdon, Mor
Averbuch, Itamar
Ziv, Oren
Brant, Boris
Elliot, Evan
Gelberg, Shachaf
Titelbaum, Moran
Koren, Omry
Avni, Orly
Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells
title Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells
title_full Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells
title_fullStr Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells
title_full_unstemmed Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells
title_short Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells
title_sort social-stress-responsive microbiota induces stimulation of self-reactive effector t helper cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517692/
https://www.ncbi.nlm.nih.gov/pubmed/31098398
http://dx.doi.org/10.1128/mSystems.00292-18
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