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Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production

Soluble flagellin (sFliC) from Salmonella Typhimurium (STm) can induce a Th2 response to itself and coadministered antigens through ligation of TLR5. These properties suggest that sFliC could potentially modulate responses to Th1 antigens like live STm if both antigens are given concurrently. After...

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Autores principales: Flores‐Langarica, Adriana, Bobat, Saeeda, Marshall, Jennifer L., Yam‐Puc, Juan Carlos, Cook, Charlotte N., Serre, Karine, Kingsley, Robert A., Flores‐Romo, Leopoldo, Uematsu, Satoshi, Akira, Shizuo, Henderson, Ian R., Toellner, Kai M., Cunningham, Adam F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973836/
https://www.ncbi.nlm.nih.gov/pubmed/26036767
http://dx.doi.org/10.1002/eji.201545564
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author Flores‐Langarica, Adriana
Bobat, Saeeda
Marshall, Jennifer L.
Yam‐Puc, Juan Carlos
Cook, Charlotte N.
Serre, Karine
Kingsley, Robert A.
Flores‐Romo, Leopoldo
Uematsu, Satoshi
Akira, Shizuo
Henderson, Ian R.
Toellner, Kai M.
Cunningham, Adam F.
author_facet Flores‐Langarica, Adriana
Bobat, Saeeda
Marshall, Jennifer L.
Yam‐Puc, Juan Carlos
Cook, Charlotte N.
Serre, Karine
Kingsley, Robert A.
Flores‐Romo, Leopoldo
Uematsu, Satoshi
Akira, Shizuo
Henderson, Ian R.
Toellner, Kai M.
Cunningham, Adam F.
author_sort Flores‐Langarica, Adriana
collection PubMed
description Soluble flagellin (sFliC) from Salmonella Typhimurium (STm) can induce a Th2 response to itself and coadministered antigens through ligation of TLR5. These properties suggest that sFliC could potentially modulate responses to Th1 antigens like live STm if both antigens are given concurrently. After coimmunization of mice with sFliC and STm there was a reduction in Th1 T cells (T‐bet(+)IFN‐γ(+) CD4 T cells) compared to STm alone and there was impaired clearance of STm. In contrast, there was no significant defect in the early extrafollicular B‐cell response to STm. These effects are dependent upon TLR5 and flagellin expression by STm. The mechanism for these effects is not related to IL‐4 induced to sFliC but rather to the effects of sFliC coimmunization on DCs. After coimmunization with STm and sFliC, splenic DCs had a lower expression of costimulatory molecules and profoundly altered kinetics of IL‐12 and TNFα expression. Ex vivo experiments using in vivo conditioned DCs confirmed the effects of sFliC were due to altered DC function during a critical window in the coordinated interplay between DCs and naïve T cells. This has marked implications for understanding how limits in Th1 priming can be achieved during infection‐induced, Th1‐mediated inflammation.
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spelling pubmed-49738362016-08-17 Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production Flores‐Langarica, Adriana Bobat, Saeeda Marshall, Jennifer L. Yam‐Puc, Juan Carlos Cook, Charlotte N. Serre, Karine Kingsley, Robert A. Flores‐Romo, Leopoldo Uematsu, Satoshi Akira, Shizuo Henderson, Ian R. Toellner, Kai M. Cunningham, Adam F. Eur J Immunol Immunity to Infection Soluble flagellin (sFliC) from Salmonella Typhimurium (STm) can induce a Th2 response to itself and coadministered antigens through ligation of TLR5. These properties suggest that sFliC could potentially modulate responses to Th1 antigens like live STm if both antigens are given concurrently. After coimmunization of mice with sFliC and STm there was a reduction in Th1 T cells (T‐bet(+)IFN‐γ(+) CD4 T cells) compared to STm alone and there was impaired clearance of STm. In contrast, there was no significant defect in the early extrafollicular B‐cell response to STm. These effects are dependent upon TLR5 and flagellin expression by STm. The mechanism for these effects is not related to IL‐4 induced to sFliC but rather to the effects of sFliC coimmunization on DCs. After coimmunization with STm and sFliC, splenic DCs had a lower expression of costimulatory molecules and profoundly altered kinetics of IL‐12 and TNFα expression. Ex vivo experiments using in vivo conditioned DCs confirmed the effects of sFliC were due to altered DC function during a critical window in the coordinated interplay between DCs and naïve T cells. This has marked implications for understanding how limits in Th1 priming can be achieved during infection‐induced, Th1‐mediated inflammation. John Wiley and Sons Inc. 2015-08 2015-06-24 /pmc/articles/PMC4973836/ /pubmed/26036767 http://dx.doi.org/10.1002/eji.201545564 Text en © 2015 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Immunity to Infection
Flores‐Langarica, Adriana
Bobat, Saeeda
Marshall, Jennifer L.
Yam‐Puc, Juan Carlos
Cook, Charlotte N.
Serre, Karine
Kingsley, Robert A.
Flores‐Romo, Leopoldo
Uematsu, Satoshi
Akira, Shizuo
Henderson, Ian R.
Toellner, Kai M.
Cunningham, Adam F.
Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production
title Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production
title_full Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production
title_fullStr Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production
title_full_unstemmed Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production
title_short Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production
title_sort soluble flagellin coimmunization attenuates th1 priming to salmonella and clearance by modulating dendritic cell activation and cytokine production
topic Immunity to Infection
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973836/
https://www.ncbi.nlm.nih.gov/pubmed/26036767
http://dx.doi.org/10.1002/eji.201545564
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