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The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection

Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typh...

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Autores principales: Darby, Matthew, Schnoeller, Corinna, Vira, Alykhan, Culley, Fiona, Bobat, Saeeda, Logan, Erin, Kirstein, Frank, Wess, Jürgen, Cunningham, Adam F., Brombacher, Frank, Selkirk, Murray E., Horsnell, William G. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309615/
https://www.ncbi.nlm.nih.gov/pubmed/25629518
http://dx.doi.org/10.1371/journal.ppat.1004636
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author Darby, Matthew
Schnoeller, Corinna
Vira, Alykhan
Culley, Fiona
Bobat, Saeeda
Logan, Erin
Kirstein, Frank
Wess, Jürgen
Cunningham, Adam F.
Brombacher, Frank
Selkirk, Murray E.
Horsnell, William G. C.
author_facet Darby, Matthew
Schnoeller, Corinna
Vira, Alykhan
Culley, Fiona
Bobat, Saeeda
Logan, Erin
Kirstein, Frank
Wess, Jürgen
Cunningham, Adam F.
Brombacher, Frank
Selkirk, Murray E.
Horsnell, William G. C.
author_sort Darby, Matthew
collection PubMed
description Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R(-/-) mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R(-/-) mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R(-/-) mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection.
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spelling pubmed-43096152015-02-06 The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection Darby, Matthew Schnoeller, Corinna Vira, Alykhan Culley, Fiona Bobat, Saeeda Logan, Erin Kirstein, Frank Wess, Jürgen Cunningham, Adam F. Brombacher, Frank Selkirk, Murray E. Horsnell, William G. C. PLoS Pathog Research Article Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R(-/-) mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R(-/-) mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R(-/-) mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection. Public Library of Science 2015-01-28 /pmc/articles/PMC4309615/ /pubmed/25629518 http://dx.doi.org/10.1371/journal.ppat.1004636 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Darby, Matthew
Schnoeller, Corinna
Vira, Alykhan
Culley, Fiona
Bobat, Saeeda
Logan, Erin
Kirstein, Frank
Wess, Jürgen
Cunningham, Adam F.
Brombacher, Frank
Selkirk, Murray E.
Horsnell, William G. C.
The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection
title The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection
title_full The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection
title_fullStr The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection
title_full_unstemmed The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection
title_short The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection
title_sort m3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309615/
https://www.ncbi.nlm.nih.gov/pubmed/25629518
http://dx.doi.org/10.1371/journal.ppat.1004636
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