Identification of Antigen-Specific Antibody Responses Associated with Upper Genital Tract Pathology in Mice Infected with Chlamydia muridarum

Abstract

Urogenital infection with Chlamydia trachomatis in some women can lead to upper genital tract pathologies, such as hydrosalpinx, potentially affecting fertility. In the current study, 27 of 40 mice intravaginally infected with Chlamydia muridarum developed visible hydrosalpinges in the oviduct while the remaining 13 did not, although all infected mice displayed similar infection time courses. Antisera from the 40 mice recognized 130 out of 257 C. muridarum proteins as antigens and 17 as immunodominant antigens. Importantly, the 27 mice with hydrosalpinges preferentially recognized two C. muridarum proteins (TC0582 and TC0912, designated pathology-associated antigens) while the 13 mice with no hydrosalpinx preferentially recognized 10 proteins (TC0047, TC0117, TC0190, TC0197, TC0257, TC0279, TC0326, TC0630, TC0689, and TC0816, designated nonpathology antigens). The preferential recognition was validated by absorption and independently confirmed in Western blots. The C. trachomatis homolog of TC0912 is encoded by a highly polymorphic gene that is associated with ocular pathogenesis. A fragment of TC0912 was found to improve the differentiation of hydrosalpinx from nonhydrosalpinx mice. TC0582 is a highly conserved ATP synthase, and it may contribute to chlamydial pathogenesis via mechanisms similar to those hypothesized for the highly conserved HSP60. Thus, we have identified chlamydial antigens and epitopes that are associated with either susceptibility or resistance to upper genital tract pathology, which will help us to further understand chlamydial pathogenesis and to develop anti- Chlamydia subunit vaccines.