Poster Presentation Lorne Infection and Immunity 2013

The Role of Interferon Epsilon in the Female Reproductive Tract. (#137)

Niamh Mangan 1 , Nollaig Bourke 1 , Hong PT Nguyen 1 , Ka Yee Fung 1 , Sebastian Stifter 1 , Caroline Gargett 1 , Paul J Hertzog 1
  1. Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia

In the female reproductive tract (FRT), homeostasis needs to be maintained to enable embryo implantation and development in parallel with priming of the immune system, which must be allowed to protect against localised infection. However, FRT is also at risk from mucosal pathogens including sexually transmitted infections (STIs) and indeed, women in the certain stages of cycle are more susceptible to STIs. Epithelial cells are the first line of defense against infections in the FRT, where they form a mucosal barrier as well as produce many cytokines and chemokines to provide a mucosal immune response, however, orchestration of this response is still poorly understood. We demonstrate here, the differential responsiveness of uterine epithelial cells (UEC) to pathogens, depending on the stage of cycle.

Type I Interferons (IFNs) are important innate cytokines in the immune response to infections, including STIs. IFN epsilon (e) is a novel type I IFN that was discovered in our laboratory and intriguingly its expression is localised in the FRT, most notably in the uterus. Importantly, using our gene targeted mice, we have demonstrated that this novel cytokine protects mice from experimental models of STIs – Chlamydia muridarum and Herpes Simplex Virus. Intriguingly, the responsiveness of the uterus to pathogens is reduced in the presence of progesterone thus providing a window of opportunity for uptake of infection. We now demonstrate that IFNe is effective in inducing a type I IFN response in UEC from women at different stages of cycle and in particular at this window of vulnerability. IFNe is constitutively expressed in the FRT unlike the other type I IFNs, thus, investigation of the role of IFNe in the FRT may identify new therapeutic strategies for manipulating the immune response in disease, through regulation of the endogenous control mechanisms.