Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.

Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting...

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Autores principales:	Adam K A Wright, Mathieu Bangert, Jenna F Gritzfeld, Daniela M Ferreira, Kondwani C Jambo, Angela D Wright, Andrea M Collins, Stephen B Gordon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/991ee9a5e40343629520074aa869eb22
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spelling	oai:doaj.org-article:991ee9a5e40343629520074aa869eb222021-11-18T06:05:51ZExperimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.1553-73661553-737410.1371/journal.ppat.1003274https://doaj.org/article/991ee9a5e40343629520074aa869eb222013-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555269/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4(+) T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4(+) T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A(+) CD4(+) T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF(+)/IL-17A(+) co-producing CD4(+) memory T-cells (p<0.01); IFNγ(+) CD4(+) memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4(+) memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = -0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4(+) memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.Adam K A WrightMathieu BangertJenna F GritzfeldDaniela M FerreiraKondwani C JamboAngela D WrightAndrea M CollinsStephen B GordonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 3, p e1003274 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Adam K A Wright Mathieu Bangert Jenna F Gritzfeld Daniela M Ferreira Kondwani C Jambo Angela D Wright Andrea M Collins Stephen B Gordon Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.
description	Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4(+) T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4(+) T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A(+) CD4(+) T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF(+)/IL-17A(+) co-producing CD4(+) memory T-cells (p<0.01); IFNγ(+) CD4(+) memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4(+) memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = -0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4(+) memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.
format	article
author	Adam K A Wright Mathieu Bangert Jenna F Gritzfeld Daniela M Ferreira Kondwani C Jambo Angela D Wright Andrea M Collins Stephen B Gordon
author_facet	Adam K A Wright Mathieu Bangert Jenna F Gritzfeld Daniela M Ferreira Kondwani C Jambo Angela D Wright Andrea M Collins Stephen B Gordon
author_sort	Adam K A Wright
title	Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.
title_short	Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.
title_full	Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.
title_fullStr	Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.
title_full_unstemmed	Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.
title_sort	experimental human pneumococcal carriage augments il-17a-dependent t-cell defence of the lung.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/991ee9a5e40343629520074aa869eb22
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Experimental human pneumococcal carriage augments IL-17A-dependent T-cell defence of the lung.

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