Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection

Host immune responses, including the characteristic influx of neutrophils, against Neisseria gonorrhoeae are poorly understood; adaptive immunity is minimal and nonprotective. We hypothesize that N. gonorrhoeae selectively elicits Th17-dependent responses which recruit innate defense mechanisms including neutrophils and antimicrobial proteins that it can resist. We found that N. gonorrhoeae induced production of IL-17 in mouse T cells and of Th17-inducing cytokines in mouse and human antigen-presenting cells in vitro. IL-17 was induced in the iliac lymph nodes in vivo in a female mouse model of genital tract gonococcal infection. Antibody blockade of IL-17 or deletion of the major IL-17 receptor in IL-17RA-knockoutmice led to prolonged infection and diminished neutrophil influx. Genital tract tissue from IL-17RA-knockout mice showed reduced production of neutrophil-attractant chemokines in response to culture with N. gonorrhoeae. These results imply a crucial role for IL-17 and Th17 cells in the immune response to N. gonorrhoeae.