Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation
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Published Version
Date
2008-08-01
Authors
O'Mahony, Caitlin
Scully, Paul
O'Mahony, David
Murphy, Sharon
O'Brien, Frances
Lyons, Anne
Sherlock, Graham
MacSharry, John
Kiely, Barry
Shanahan, Fergus
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS
Published Version
Abstract
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-kB 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-kB 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 naı¨ve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kB 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-kB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kB 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.
Description
Keywords
Regulatory T Cells , Bifidobacterium infantis , Salmonella typhimurium , Commensal , Pathogen , NF-kB
Citation
O’Mahony C, Scully P, O’Mahony D, Murphy S, O’Brien F, et al. (2008) Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-kB Activation. PLoS Pathog 4(8): e1000112. doi:10.1371/journal.ppat.1000112