Identification of collaborative cross mouse strains susceptible to chlamydial induction of hydrosalpinx

Sexually transmitted infection with <i>Chlamydia trachomatis</i> can cause pathology, such as hydrosalpinx, in the upper genital tract, leading to infertility. To investigate how genetic variation affects chlamydial pathogenicity, we screened five strains of Collaborative Cross (CC) mice for susceptibility to intravaginal infection and hydrosalpinx induction by <i>C. muridarum</i>, a mouse-adapted chlamydial species used extensively to reveal chlamydial pathogenic mechanisms. In terms of susceptibility to genital chlamydial infection, the five CC strains fell into two categories: CC011 and CC012 were resistant, while CC037, CC042, and CC080 were susceptible. The resistant strains shed significant levels of live organisms from the genital tract for only ~2 weeks, whereas the susceptible strains shed for ~4 weeks. However, the resistant CC012 mice developed the highest level of hydrosalpinx, while the susceptible CC042 mice were fully resistant to hydrosalpinx induction. None of the CC mice developed spontaneous hydrosalpinx in the absence of chlamydial infection. The above results, validated macroscopically and microscopically, indicate no correlation between pathology and genital infection, as observed in other inbred mice. Nevertheless, among the two infection-resistant strains, CC012 developed more severe hydrosalpinx than CC011, and hydrosalpinx was positively correlated with live organism shedding from rectal swabs but not from vaginal swabs, supporting a potential role of gastrointestinal chlamydia in chlamydial genital pathogenicity. The above results lay a foundation for using CC mice to further map the genetic determinants that regulate host susceptibility to chlamydial infection and pathogenicity in the female genital tract.