Intravaginal Chlamydia trachomatis Challenge Infection Elicits T(H)1 and T(H)17 Immune Responses in Mice That Promote Pathogen Clearance and Genital Tract Damage

While ascension of Chlamydia trachomatis into the upper genital tract of women can cause pelvic inflammatory disease and Fallopian tube damage, most infections elicit no symptoms or overt upper genital tract pathology. Consistent with this asymptomatic clinical presentation, genital C. trachomatis infection of women generates robust T(H)2 immunity. As an animal model that modeled this response would be invaluable for delineating bacterial pathogenesis and human host defenses, herein we explored if pathogen-specific T(H)2 immunity is similarly elicited by intravaginal (ivag) infection of mice with oculogenital C. trachomatis serovars. Analogous to clinical infection, ascension of primary C. trachomatis infection into the mouse upper genital tract produced no obvious tissue damage. Clearance of ivag challenge infection was mediated by interferon (IFN)-γ-producing CD4(+) T cells, while IFN-γ signaling blockade concomitant with a single ivag challenge promoted tissue damage by enhancing Chlamydia-specific T(H)17 immunity. Likewise, IFN-γ and IL-17 signaling blockade or CD4(+) T cell depletion eliminated the genital pathology produced in untreated controls by multiple ivag challenge infections. Conversely, we were unable to detect formation of pathogen-specific T(H)2 immunity in C. trachomatis-infected mice. Together, our work revealed C. trachomatis infection of mice generates T(H)1 and T(H)17 immune responses that promote pathogen clearance and immunopathological tissue damage. Absence of Chlamydia-specific T(H)2 immunity in these mice newly highlights the need to identify experimental models of C. trachomatis genital infection that more closely recapitulate the human host response.