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Interleukin-17A mediates acquired immunity to pneumococcal colonization

Lu, YJ and Gross, J and Bogaert, D and Finn, A and Bagrade, L and Zhang, Q and Kolls, JK and Srivastava, A and Lundgren, A and Forte, S and Thompson, CM and Harney, KF and Anderson, PW and Lipsitch, M and Malley, R (2008) Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathogens, 4 (9). ISSN 1553-7366

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Abstract

Although anticapsular antibodies confer serotype-specific immunity to pneumococci, children increase their ability to clear colonization before these antibodies appear, suggesting involvement of other mechanisms. We previously reported that intranasal immunization of mice with pneumococci confers CD4+ T cell-dependent, antibody- and serotype-independent protection against colonization. Here we show that this immunity, rather than preventing initiation of carriage, accelerates clearance over several days, accompanied by neutrophilic infiltration of the nasopharyngeal mucosa. Adoptive transfer of immune CD4+ T cells was sufficient to confer immunity to naïve RAG1 -/- mice. A critical role of interleukin (IL)-17A was demonstrated: mice lacking interferon-γ or IL-4 were protected, but not mice lacking IL-17A receptor or mice with neutrophil depletion. In vitro expression of IL-17A in response to pneumococci was assayed: lymphoid tissue from vaccinated mice expressed significantly more IL-17A than controls, and IL-17A expression from peripheral blood samples from immunized mice predicted protection in vivo. IL-17A was elicited by pneumococcal stimulation of tonsillar cells of children or adult blood but not cord blood. IL-17A increased pneumococcal killing by human neutrophils both in the absence and in the presence of antibodies and complement. We conclude that IL-17A mediates pneumococcal immunity in mice and probably in humans; its elicitation in vitro could help in the development of candidate pneumococcal vaccines. © 2008 Lu et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lu, YJ
Gross, J
Bogaert, D
Finn, A
Bagrade, L
Zhang, Q
Kolls, JKjkk23@pitt.eduJKK23
Srivastava, A
Lundgren, A
Forte, S
Thompson, CM
Harney, KF
Anderson, PW
Lipsitch, M
Malley, R
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorPhilpott, Dana J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 September 2008
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 4
Number: 9
DOI or Unique Handle: 10.1371/journal.ppat.1000159
Refereed: Yes
ISSN: 1553-7366
PubMed Central ID: PMC2528945
PubMed ID: 18802458
Date Deposited: 24 Jul 2012 18:46
Last Modified: 19 Jun 2021 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/12998

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