TNF-alpha receptors 1 and 2 contribute to the development of upper genital tract pathology following primary genital chlamydia muridarum infection in mice (P3200)

Abstract

Abstract Chlamydia is the leading cause of sexually transmitted disease worldwide and causes serious pathologies in the upper reproductive tract. In this study, we evaluated the contribution of TNF receptor 1 (TNFR1) and TNFR2 to upper genital tract pathogenesis following primary intravaginal chlamydial infection in mice deficient in TNFR1 (TNFR1 KO), TNFR2 (TNFR2 KO), or TNFR1 and 2 (TNFR1/2 DKO), and the corresponding C57BL/6J wild type mice. All groups (n=8) of mice displayed comparable chlamydial clearance following primary bacterial inoculation. The production of IFN-gamma, IL-5, TNF-alpha, and IL-1 beta in the genital tracts, draining iliac lymph nodes, and spleens on day 9 following inoculation were comparable in all the groups. Serum anti-Chlamydia total Ab, IgG2c, and IgG1 response on days 14 and 60 following primary inoculation were comparable in all the groups. On day 80 after primary incoluation, TNFR1 KO, TNFR2 KO, and TNFR1/2 DKO mice displayed significantly reduced hydrosalpinx (6 %, 44%, and 0% oviducts, respectively), when compared to C57BL/6J mice (75% oviducts). Anti-Chlamydia antibody response and bacterial clearance following secondary intravaginal C. muridarum infection was comparable in all groups of mice. Collectively, these results suggest that TNFR1 and TNFR2 do not contribute significantly to chlamydial clearance, but both TNFR1 and TNFR2, with a dominant role for TNFR1, contribute to the UGT pathology following primary genital chlamydial infection.