Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the...

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Autores principales:	Carolina Perdomo, Ulrike Zedler, Anja A. Kühl, Laura Lozza, Philippe Saikali, Leif E. Sander, Alexis Vogelzang, Stefan H. E. Kaufmann, Andreas Kupz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cec34d180c4d431fa8b85707529ae45e
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spelling	oai:doaj.org-article:cec34d180c4d431fa8b85707529ae45e2021-11-15T15:50:15ZMucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis10.1128/mBio.01686-162150-7511https://doaj.org/article/cec34d180c4d431fa8b85707529ae45e2016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01686-16https://doaj.org/toc/2150-7511ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. IMPORTANCE BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the mechanisms of protection have remained elusive. Here we performed an in-depth analysis to dissect the immunological mechanisms associated with superior mucosal protection in the mouse model of TB. We found that mucosal, and not subcutaneous, BCG vaccination generates lung-resident memory T cell populations that confer protection against pulmonary TB. We establish a comprehensive phenotypic characterization of these populations, providing a framework for future vaccine development.Carolina PerdomoUlrike ZedlerAnja A. KühlLaura LozzaPhilippe SaikaliLeif E. SanderAlexis VogelzangStefan H. E. KaufmannAndreas KupzAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Carolina Perdomo Ulrike Zedler Anja A. Kühl Laura Lozza Philippe Saikali Leif E. Sander Alexis Vogelzang Stefan H. E. Kaufmann Andreas Kupz Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis
description	ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. IMPORTANCE BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the mechanisms of protection have remained elusive. Here we performed an in-depth analysis to dissect the immunological mechanisms associated with superior mucosal protection in the mouse model of TB. We found that mucosal, and not subcutaneous, BCG vaccination generates lung-resident memory T cell populations that confer protection against pulmonary TB. We establish a comprehensive phenotypic characterization of these populations, providing a framework for future vaccine development.
format	article
author	Carolina Perdomo Ulrike Zedler Anja A. Kühl Laura Lozza Philippe Saikali Leif E. Sander Alexis Vogelzang Stefan H. E. Kaufmann Andreas Kupz
author_facet	Carolina Perdomo Ulrike Zedler Anja A. Kühl Laura Lozza Philippe Saikali Leif E. Sander Alexis Vogelzang Stefan H. E. Kaufmann Andreas Kupz
author_sort	Carolina Perdomo
title	Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis
title_short	Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis
title_full	Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis
title_fullStr	Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis
title_full_unstemmed	Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis
title_sort	mucosal bcg vaccination induces protective lung-resident memory t cell populations against tuberculosis
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/cec34d180c4d431fa8b85707529ae45e
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Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

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