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Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection

Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin(+) CD8α(+) dendritic cells (DCs), residing in the marginal zone of the murine splee...

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Autores principales: Prendergast, Kelly A., Daniels, Naomi J., Petersen, Troels R., Hermans, Ian F., Kirman, Joanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949331/
https://www.ncbi.nlm.nih.gov/pubmed/29867941
http://dx.doi.org/10.3389/fimmu.2018.00953
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author Prendergast, Kelly A.
Daniels, Naomi J.
Petersen, Troels R.
Hermans, Ian F.
Kirman, Joanna R.
author_facet Prendergast, Kelly A.
Daniels, Naomi J.
Petersen, Troels R.
Hermans, Ian F.
Kirman, Joanna R.
author_sort Prendergast, Kelly A.
collection PubMed
description Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin(+) CD8α(+) dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8(+) T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilizing mice that express the diphtheria toxin receptor under control of the langerin promoter, we investigated the impact of depleting langerin(+) CD8α(+) DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette–Guerin (BCG). In the absence of langerin(+) CD8α(+) DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8(+) T cell activation, proliferation, and IFN-γ production was evident. Our data revealed that langerin(+) CD8α(+) DCs play a pivotal role in initiating CD8(+) T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections.
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spelling pubmed-59493312018-06-04 Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection Prendergast, Kelly A. Daniels, Naomi J. Petersen, Troels R. Hermans, Ian F. Kirman, Joanna R. Front Immunol Immunology Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin(+) CD8α(+) dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8(+) T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilizing mice that express the diphtheria toxin receptor under control of the langerin promoter, we investigated the impact of depleting langerin(+) CD8α(+) DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette–Guerin (BCG). In the absence of langerin(+) CD8α(+) DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8(+) T cell activation, proliferation, and IFN-γ production was evident. Our data revealed that langerin(+) CD8α(+) DCs play a pivotal role in initiating CD8(+) T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections. Frontiers Media S.A. 2018-05-07 /pmc/articles/PMC5949331/ /pubmed/29867941 http://dx.doi.org/10.3389/fimmu.2018.00953 Text en Copyright © 2018 Prendergast, Daniels, Petersen, Hermans and Kirman. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Prendergast, Kelly A.
Daniels, Naomi J.
Petersen, Troels R.
Hermans, Ian F.
Kirman, Joanna R.
Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection
title Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection
title_full Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection
title_fullStr Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection
title_full_unstemmed Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection
title_short Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection
title_sort langerin(+) cd8α(+) dendritic cells drive early cd8(+) t cell activation and il-12 production during systemic bacterial infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949331/
https://www.ncbi.nlm.nih.gov/pubmed/29867941
http://dx.doi.org/10.3389/fimmu.2018.00953
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