IRIS publication 722687
Commensal-Induced Regulatory T Cells Mediate Protection Against Pathogen-Stimulated Nf-Kappa B Activation
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TY - JOUR - O'Mahony, C, Scully, P, O'Mahony, D, Murphy, S, O'Brien, F, Lyons, A, Sherlock, G, MacSharry, J, Kiely, B, Shanahan, F, O'Mahony, L - 2008 - August - Plos Pathogens - Commensal-Induced Regulatory T Cells Mediate Protection Against Pathogen-Stimulated Nf-Kappa B Activation - Validated - () - 4 - 8 - 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-kappa B 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-kappa B 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 naive animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappa B 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-kappa B inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappa B 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.. - DOI 10.1371/journal.ppat.1000112 DA - 2008/08 ER -
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@article{V722687, = {O'Mahony, C and Scully, P and O'Mahony, D and Murphy, S and O'Brien, F and Lyons, A and Sherlock, G and MacSharry, J and Kiely, B and Shanahan, F and O'Mahony, L }, = {2008}, = {August}, = {Plos Pathogens}, = {Commensal-Induced Regulatory T Cells Mediate Protection Against Pathogen-Stimulated Nf-Kappa B Activation}, = {Validated}, = {()}, = {4}, = {8}, = {{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-kappa B 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-kappa B 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 naive animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappa B 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-kappa B inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappa B 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..}}, = {DOI 10.1371/journal.ppat.1000112}, source = {IRIS} }
Data as stored in IRIS
AUTHORS | O'Mahony, C, Scully, P, O'Mahony, D, Murphy, S, O'Brien, F, Lyons, A, Sherlock, G, MacSharry, J, Kiely, B, Shanahan, F, O'Mahony, L | ||
YEAR | 2008 | ||
MONTH | August | ||
JOURNAL_CODE | Plos Pathogens | ||
TITLE | Commensal-Induced Regulatory T Cells Mediate Protection Against Pathogen-Stimulated Nf-Kappa B Activation | ||
STATUS | Validated | ||
TIMES_CITED | () | ||
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VOLUME | 4 | ||
ISSUE | 8 | ||
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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-kappa B 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-kappa B 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 naive animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappa B 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-kappa B inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappa B 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.. | ||
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DOI_LINK | DOI 10.1371/journal.ppat.1000112 | ||
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