Invariant and Diverse NKT Cells Regulate Bacterial Clearance and Pathology in Chlamydial Genital Tract Infection in Mice.

Chlamydia trachomatis infection causes pelvic inflammatory disease and infertility, but how host immune factors control pathogen clearance or pathology is not fully understood. Using a mouse model of genital tract infection with Chlamydia muridarum, we examined the role of CD1d-restricted Natural killer T (NKT) cells. Invariant NKT cell-deficient mice (Jα18-/-) showed prolonged vaginal shedding of infectious elementary bodies (EBs), delayed clearance, and decreased early cytokine production compared to wild-type (WT) controls. Conversely, CD1d-/- mice, which lack both invariant and diverse NKT cells, did not show significant differences in vaginal shedding compared to WT mice. Surprisingly, both NKT-deficient mice (Jα18-/- and CD1d-/-) produced higher levels of inflammatory cytokines in the oviduct at day 35 post-infection (p.i.) and experienced more frequent upper genital tract pathology (hydrosalpinx) at day 80 p.i. However, no infectious EBs were recovered from the oviducts or uterine horns of NKT-deficient mice after day 35 p.i. Cortisone acetate reactivated infectious shedding in chronically infected NKT-deficient mice at day 100 p.i. These findings highlight distinct roles for NKT cell subsets: invariant NKT cells promote early clearance via rapid cytokine production, while the broader NKT population helps limit tissue damage. Targeting NKT pathways could help prevent chronic infection and infertility.