Interleukin-17A Mediates Acquired Immunity to Pneumococcal Colonization

Abstract

Although anticapsular antibodies confer serotype-specific immunity to pneumococci, children increase their ability to clear
\ncolonization before these antibodies appear, suggesting involvement of other mechanisms. We previously reported that
\nintranasal immunization of mice with pneumococci confers CD4+ T cell–dependent, antibody- and serotype-independent
\nprotection against colonization. Here we show that this immunity, rather than preventing initiation of carriage, accelerates
\nclearance over several days, accompanied by neutrophilic infiltration of the nasopharyngeal mucosa. Adoptive transfer of
\nimmune CD4+ T cells was sufficient to confer immunity to naı¨ve RAG12/2 mice. A critical role of interleukin (IL)-17A was
\ndemonstrated: mice lacking interferon-c or IL-4 were protected, but not mice lacking IL-17A receptor or mice with
\nneutrophil depletion. In vitro expression of IL-17A in response to pneumococci was assayed: lymphoid tissue from
\nvaccinated mice expressed significantly more IL-17A than controls, and IL-17A expression from peripheral blood samples
\nfrom immunized mice predicted protection in vivo. IL-17A was elicited by pneumococcal stimulation of tonsillar cells of
\nchildren or adult blood but not cord blood. IL-17A increased pneumococcal killing by human neutrophils both in the
\nabsence and in the presence of antibodies and complement. We conclude that IL-17A mediates pneumococcal immunity in
\nmice and probably in humans; its elicitation in vitro could help in the development of candidate pneumococcal vaccines.