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The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis

BACKGROUND: Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNγ in the host response to Francisella tularensis infection. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence f...

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Autores principales: Markel, Gal, Bar-Haim, Erez, Zahavy, Eran, Cohen, Hila, Cohen, Ofer, Shafferman, Avigdor, Velan, Baruch
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887844/
https://www.ncbi.nlm.nih.gov/pubmed/20585449
http://dx.doi.org/10.1371/journal.pone.0011176
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author Markel, Gal
Bar-Haim, Erez
Zahavy, Eran
Cohen, Hila
Cohen, Ofer
Shafferman, Avigdor
Velan, Baruch
author_facet Markel, Gal
Bar-Haim, Erez
Zahavy, Eran
Cohen, Hila
Cohen, Ofer
Shafferman, Avigdor
Velan, Baruch
author_sort Markel, Gal
collection PubMed
description BACKGROUND: Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNγ in the host response to Francisella tularensis infection. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary γδ and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.1×LD(50) resulted in a fatal disease. CONCLUSION: In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia.
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spelling pubmed-28878442010-06-22 The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis Markel, Gal Bar-Haim, Erez Zahavy, Eran Cohen, Hila Cohen, Ofer Shafferman, Avigdor Velan, Baruch PLoS One Research Article BACKGROUND: Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNγ in the host response to Francisella tularensis infection. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary γδ and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.1×LD(50) resulted in a fatal disease. CONCLUSION: In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia. Public Library of Science 2010-06-18 /pmc/articles/PMC2887844/ /pubmed/20585449 http://dx.doi.org/10.1371/journal.pone.0011176 Text en Markel et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Markel, Gal
Bar-Haim, Erez
Zahavy, Eran
Cohen, Hila
Cohen, Ofer
Shafferman, Avigdor
Velan, Baruch
The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
title The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
title_full The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
title_fullStr The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
title_full_unstemmed The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
title_short The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
title_sort involvement of il-17a in the murine response to sub-lethal inhalational infection with francisella tularensis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887844/
https://www.ncbi.nlm.nih.gov/pubmed/20585449
http://dx.doi.org/10.1371/journal.pone.0011176
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