Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-κB Activation

PLoS Pathogens

Sharon Murphy¹  David O'Mahony¹  John MacSharry¹  Barry Kiely¹  Graham Sherlock¹  Anne Lyons¹  Frances O'Brien¹  Paul Scully²  Caitlin O'Mahony²  Fergus Shanahan²  Liam O'Mahony² 

[1] Alimentary Health Ltd., University College Cork, Cork, Ireland;Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

关键词: Transcription factors;    T cells;    Salmonella typhimurium;    Salmonellosis;    Regulatory T cells;    Dendritic cells;    Cytokines;    Salmonella;   

DOI  :  10.1371/journal.ppat.1000112

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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-κB 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-κB 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-κB 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-κB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-κB 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.

【 授权许可】

CC BY