Male IgG Seroconversion to Urogenital Chlamydial Infection Exacerbates Immunopathology in Females

Urogenital Chlamydia trachomatis infects over 100 million people per annum and can cause inflammation, scarring, pelvic inflammatory disease and infertility in women. However, infections are often asymptomatic with an unknown underlying trigger for immunopathology. Male IgG serostatus to C. trachomatis is also a correlate of the disease outcome of female partners in fertility clinics. Using IgG purified from chronically C. muridarum-infected male mice, the role of IgG and Chlamydia in transcytosis, cellular uptake, antigen presentation and immune responses was determined in female mice. Opsonization of chlamydia with IgG enhanced uterine epithelial transcytosis of infectious Chlamydia to the lamina propria, which increased phagocytosis, antigen processing/presentation and draining lymph node migration of DCs. Primed DCs in the lymph node then expanded more CD4+ and CD8+ T cells. The expansion of T cells did not assist in host clearance of chlamydial shedding, but surprisingly enhanced fallopian tube scarring and blockage, dependent of chlamydial opsonization with IgG. When FcRn-/- mice were infected with opsonized Chlamydia the enhancement of pathology was abrogated and the infection was resolved 50% quicker. When female mice were depleted of CD8+ T cells prior to infection, FcRn-/- mice (but not FcRn+/+ mice) had a 61% reduction in the incidence of infertility. Taken together, these data demonstrate that opsonization of Chlamydia with male IgG exacerbates epithelial transcytosis, dendritic cell priming, production of immunopathogenic CD8+ T cells, and infertility in mice. These results in some part may help to explain the asymptomatic nature of Chlamydia-induced pathology and infertility in human females.