title: Interleukin-17A mediates acquired immunity to pneumococcal colonization.
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-gamma 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Children's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Jane
authors.initials: J
authors.lastname: Gross
authors.forename: Debby
authors.initials: D
authors.lastname: Bogaert
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.forename: Linda
authors.initials: L
authors.lastname: Bagrade
authors.forename: Qibo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Amit
authors.initials: A
authors.lastname: Srivastava
authors.forename: Anna
authors.initials: A
authors.lastname: Lundgren
authors.forename: Sophie
authors.initials: S
authors.lastname: Forte
authors.forename: Claudette M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Harney
authors.forename: Porter W
authors.initials: PW
authors.lastname: Anderson
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
authors.forename: Richard
authors.initials: R
authors.lastname: Malley
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002648:Child; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D020381:Interleukin-17