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dc.contributor.authorGross, Jane
dc.contributor.authorBogaert, Debby
dc.contributor.authorFinn, Adam
dc.contributor.authorBagrade, Linda
dc.contributor.authorZhang, Qibo
dc.contributor.authorKolls, Jay K.
dc.contributor.authorLundgren, Anna
dc.contributor.authorForte, Sophie
dc.contributor.authorLu, Ying-Jie
dc.contributor.authorSrivastava, Amit Kumar
dc.contributor.authorThompson, Claudette M.
dc.contributor.authorHarney, Kathleen
dc.contributor.authorAnderson, Porter
dc.contributor.authorLipsitch, Marc
dc.contributor.authorMalley, Richard
dc.date.accessioned2010-11-08T19:51:44Z
dc.date.issued2008
dc.identifier.citationLu, Ying-Jie, Jane Gross, Debby Bogaert, Adam Finn, Linda Bagrade, Qibo Zhang, Jay K. Kolls, et al. 2008. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathogens 4(9): e1000159.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4551755
dc.description.abstractAlthough 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1000159en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528945/pdf/en_US
dash.licenseLAA
dc.subjectimmunologyen_US
dc.subjectimmune responseen_US
dc.subjectinfectious diseasesen_US
dc.subjectbacterial infectionsen_US
dc.titleInterleukin-17A Mediates Acquired Immunity to Pneumococcal Colonizationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorLipsitch, Marc
dc.date.available2010-11-08T19:51:44Z
dash.affiliation.otherSPH^Epidemiologyen_US
dc.identifier.doi10.1371/journal.ppat.1000159*
dash.authorsorderedfalse
dash.contributor.affiliatedLu, Ying-Jie
dash.contributor.affiliatedHarney, Kathleen
dash.contributor.affiliatedAnderson, Porter
dash.contributor.affiliatedThompson, Claudette
dash.contributor.affiliatedMalley, Richard
dash.contributor.affiliatedSrivastava, Amit
dash.contributor.affiliatedLipsitch, Marc


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