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-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.

IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

“…It argues against a direct killing effect of the cytokine or contaminant present in the cytokine preparation. Our findings corroborate those of others showing that IL-17 potentiates in vitro neutrophil killing of pneumococcus (55). However, they are in apparent contradiction with the demonstration that IL-17 reduces neutrophil antifungal activity (56).…”

Cytokine responses in primary and secondary respiratory syncytial virus infections

“…The potential role of Articles TH17 cells in contributing to protection against repeated infection was also highlighted in a study which demonstrated that the RSV NS1protein, which acts as an interferon antagonist, specifically suppresses proliferation and activation of both CD103+CD8+ cells and TH17 cells (37). While there has been much interest in the role of IL-17 in the pathogenesis of chronic, autoimmune diseases such as rheumatoid arthritis, it also appears to have a beneficial role in acute bacterial infections such as those due to pneumococcal pneumonia (13,14). Little is known about its role in respiratory viral infections.…”

“…Data from studies involving other pulmonary pathogens such as Streptococcus pneumonia suggest that the release of interleukin (IL-17) from CD4 T cells (TH17) is extremely important in enhancing the ability of neutrophils to kill the organisms in the airways (13,14). Hence, the generation of pathogen-specific IL-17 cells may be an important component of effective secondary responses to respiratory pathogens (15).…”

The Capsular Serotype ofStreptococcus pneumoniaeIs More Important than the Genetic Background for Resistance to Complement

“…Once invasive disease is established, heavily encapsulated bacteria are better protected from phagocytes (22). If clearance of pneumococci from the nasopharynx is mediated by T cells (25,50), the ability of pneumococcal serotypes to persist in the nasopharynx would depend on their ability to resist killing by neutrophils (51). Heavily encapsulated serotypes were found to be more resistant to nonopsonic phagocytosis by neutrophils, and it was suggested that the structure of the capsular polysaccharide would determine the success of a serotype during nasopharyngeal carriage (51).…”