Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-β-dependent mechanisms

Infection with Neisseria gonorrhoeae does not induce specific immunity or immune memory. Our previous studies in a murine model of vaginal gonococcal infection showed that innate immunity governed by Th17 cells was a critical aspect of the immune response elicited by this pathogen. Herein we show that N. gonorrhoeae selectively inhibited Th1 and Th2 cells and enhanced Th17 cell development through the induction of TGF-beta. Whereas Th17 responses depended on gonococcal lipooligosaccharide acting through TLR4, the inhibitory effect of N. gonorrhoeae on Th1/Th2 responses involved gonococcal Opa proteins. In vitro Th17 responses to N. gonorrhoeae could be diverted to Th1/Th2 by blockade of TGF-beta, but not by blockade of IL-17. The results reveal that N. gonorrhoeae suppresses Th1/Th2-mediated adaptive immune response through mechanisms dependent on TGF-beta, and that this effect can be manipulated to promote the development of adaptive immunity.