Role of NK cells in IFN-epsilon-mediated protection against female reproductive tract infection (MUC2P.925)

• Published in: The Journal of immunology (1950) 2015-05, Vol.194 (1_Supplement), p.65-65.8
• Main Authors: Hansbro, Philip, Mayall, Jemma, Mangan, Niamh, Starkey, Malcolm, Kim, Richard, Hertzog, Paul, Horvat, Jay
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.194.Supp.65.8

Chlamydia trachomatis is the most common bacterial STI and frequently results in reproductive tract (RT) sequelae such as pelvic inflammatory disease and infertility. However, the immune processes involved in the clearance and immunopathology of Chlamydia infection are not well understood. In previous studies we showed that IFN-ε, a novel type I IFN that is exclusively and constitutively expressed in the female RT, plays an important role in protecting against Chlamydia infections. Here, we examined the effects of IFN-ɛ on cellular responses in the female RT in order to elucidate the mechanisms by which IFN-ɛ protects against Chlamydia infections. Female WT and IFN-ε-/- C57BL/6 mice were pre-treated with progesterone and infected intra-vaginally with Chlamydia muridarum or sham-infected. Uterine horns were harvested and the effects of IFN-ε deficiency on Chlamydia infection, immune factor expression and cellular infiltration were assessed using real-time qPCR and flow cytometry. We show that IFN-ε-/- mice have increased Chlamydia 16S expression in the upper RT which correlated with fewer NK cells and tissue-resident uterine NK cells at 3 days post infection. IFN-γ+ CD45+ cells were also decreased in the infected IFN-ε-/- mice, of which over 60% were NK cells. These changes were associated with reduced iNOS and STAT1 expression. These findings suggest that IFN-ε may protect against Chlamydia RT infections by potentiating the recruitment of protective IFN-γ-producing NK cells.