Primary fallopian tube epithelial cells are resistant to Chlamydia trachomatis infection due to high expression of ido1.

Abstract

Abstract Chlamydia trachomatis (Ct) is the most prevalent sexually transmitted bacterial infection in the world. In ~50% of cisgender women, Ct ascends from the cervix to infect the upper genital tract and increased ascension is linked to hormonal therapies. Oviduct infection induces inflammation which can lead to tubal scarring and sequelae of infertility and ectopic pregnancy. Fortunately, these complications occur in a minority of infected women, suggesting that intrinsic factors may protect the fallopian tubes from infection or tissue damage. In vitro inoculation of primary fallopian tube epithelial (FTE) cells with Ct serovar E resulted in a 10-fold reduction in infected cells compared to transformed endocervical HeLa cells. Indoleamine 2,3-dioxygenase (IDO) in the cytoplasm of epithelial cells acts as a key mediator of chlamydial host defense by metabolizing tryptophan, an essential Ct nutrient. We determined that uninfected primary FTE cells expressed on average 9 times higher levels of ido1 transcripts by qPCR compared to HeLa cells, and that in vitro infectivity of FTE cells was rescued by addition of an IDO-inhibitor (9-fold), tryptophan (21-fold), or indole (a metabolite that bypasses tryptophan starvation; 16-fold). Induction of IDO has mostly been attributed to IFNγ, but it can also be induced by Type I IFNs. Detection of high constitutive ido1 transcription in primary FTE cells indicates their ability to produce IDO independently of IFNγ. Ongoing studies are examining the role of Type I IFNs, including IFNɛ, which is constitutively expressed by reproductive tract epithelium and regulated by hormones. This work has implications for defining factors that contribute to protection of women from Ct-induced disease. The study was funded through a Translational Team Science Award (UNC School of Medicine and NC TRaCS) and also funded by NIAID NIH R01 AI067678 to U.M.N., NIAID NIH R01 AI119164 to T.D., and NIH grant DK065988 and Cystic Fibrosis Foundation grant BOUCHE15R0 to S.H.R.