Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that...

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Autores principales:	Adam K A Wright, Daniela M Ferreira, Jenna F Gritzfeld, Angela D Wright, Kathryn Armitage, Kondwani C Jambo, Emily Bate, Sherouk El Batrawy, Andrea Collins, Stephen B Gordon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/66e905982c694e28a711f28005765625
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spelling	oai:doaj.org-article:66e905982c694e28a711f280057656252021-11-18T06:04:34ZHuman nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.1553-73661553-737410.1371/journal.ppat.1002622https://doaj.org/article/66e905982c694e28a711f280057656252012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496648/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans.Adam K A WrightDaniela M FerreiraJenna F GritzfeldAngela D WrightKathryn ArmitageKondwani C JamboEmily BateSherouk El BatrawyAndrea CollinsStephen B GordonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 4, p e1002622 (2012)
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 Daniela M Ferreira Jenna F Gritzfeld Angela D Wright Kathryn Armitage Kondwani C Jambo Emily Bate Sherouk El Batrawy Andrea Collins Stephen B Gordon Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
description	Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans.
format	article
author	Adam K A Wright Daniela M Ferreira Jenna F Gritzfeld Angela D Wright Kathryn Armitage Kondwani C Jambo Emily Bate Sherouk El Batrawy Andrea Collins Stephen B Gordon
author_facet	Adam K A Wright Daniela M Ferreira Jenna F Gritzfeld Angela D Wright Kathryn Armitage Kondwani C Jambo Emily Bate Sherouk El Batrawy Andrea Collins Stephen B Gordon
author_sort	Adam K A Wright
title	Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
title_short	Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
title_full	Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
title_fullStr	Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
title_full_unstemmed	Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
title_sort	human nasal challenge with streptococcus pneumoniae is immunising in the absence of carriage.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/66e905982c694e28a711f28005765625
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Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.

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