Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota comp...

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Autores principales:	Caitlin O'Mahony, Paul Scully, David O'Mahony, Sharon Murphy, Frances O'Brien, Anne Lyons, Graham Sherlock, John MacSharry, Barry Kiely, Fergus Shanahan, Liam O'Mahony
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0dc4c292be4a45c794aaf326bd202405
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spelling	oai:doaj.org-article:0dc4c292be4a45c794aaf326bd2024052021-11-25T05:46:29ZCommensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.1553-73661553-737410.1371/journal.ppat.1000112https://doaj.org/article/0dc4c292be4a45c794aaf326bd2024052008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18670628/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.Caitlin O'MahonyPaul ScullyDavid O'MahonySharon MurphyFrances O'BrienAnne LyonsGraham SherlockJohn MacSharryBarry KielyFergus ShanahanLiam O'MahonyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 8, p e1000112 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Caitlin O'Mahony Paul Scully David O'Mahony Sharon Murphy Frances O'Brien Anne Lyons Graham Sherlock John MacSharry Barry Kiely Fergus Shanahan Liam O'Mahony Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.
description	Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.
format	article
author	Caitlin O'Mahony Paul Scully David O'Mahony Sharon Murphy Frances O'Brien Anne Lyons Graham Sherlock John MacSharry Barry Kiely Fergus Shanahan Liam O'Mahony
author_facet	Caitlin O'Mahony Paul Scully David O'Mahony Sharon Murphy Frances O'Brien Anne Lyons Graham Sherlock John MacSharry Barry Kiely Fergus Shanahan Liam O'Mahony
author_sort	Caitlin O'Mahony
title	Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.
title_short	Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.
title_full	Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.
title_fullStr	Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.
title_full_unstemmed	Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.
title_sort	commensal-induced regulatory t cells mediate protection against pathogen-stimulated nf-kappab activation.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/0dc4c292be4a45c794aaf326bd202405
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Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

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