IMMUNITY TO CHLAMYDIA-TRACHOMATIS IS MEDIATED BY T-HELPER-1 CELLS THROUGH IFN-GAMMA-DEPENDENT AND IFN-GAMMA-INDEPENDENT PATHWAYS

Mucosal immunity to Chlamydia trachomatis in a mouse model of female g enital tract infection is mediated predominantly by Th1-type cells, as shown by in vivo neutralization of cytokines involved in the Th1 vs T h2 pathways. Neutralization of IL-12 was associated with an apparent d ecrease in the infiltration of CD4(+) T cells into infected tissues, s ystemic reductions in the production of IFN-gamma, and prolonged shedd ing of high levels of bacteria. Neutralization of IL-4 had no detectab le effect on host immunity or on bacterial clearance. To dissociate th e protective role of IL-12 from that of IL-12-induced IFN-gamma, resis tance to C. trachomatis was compared in IL-12-depleted and IFN-gamma-d eficient animals. IL-12-depleted mice displayed minimal bacterial clea rance for 1 mo post-infection but eventually resolved genital tract in fections completely. IFN-gamma-deficient mice, on the other hand, clea red 99.9% of genital Chlamydia within the first 3 wk but then develope d systemic disease associated with dissemination of bacteria to multip le organs, Animals surviving this stage often maintained low level per sistent infections within the urogenital tract. These results indicate that the bulk of chlamydial clearance from the genital mucosa is medi ated by an IL-12-dependent, IFN-gamma-independent mechanism, while pre vention of disseminated disease requires the action of IFN-gamma.