Sex hormone modulation of human uterine epithelial cell immune responses

Sexually transmitted infections are a major worldwide publichealth problem affecting millions of people. A number of bacteria,fungi, viruses, and protozoa can infect reproductive tissues,resulting in varying degrees of pathology ranging from littlediscomfort to death. The female reproductive tract has evolvedinnate and adaptive immune mechanisms that protect from microbialinfection, thereby reducing infection and disease. Central tothis protection are the epithelial cells that line the femalereproductive tract. In the uterus, columnar epithelial cellsprovide a physical barrier to microbial infection, possess toll-likereceptors that detect pathogens and secrete a number of constitutiveand induced factors that directly or indirectly hinder infection.For example, uterine epithelial cells secrete peptides thatdestroy pathogenic microbes. In addition, epithelial cells producechemokines and cytokines that attract and activate innate immunecells and serve as a link to the adaptive immune system. Further,uterine epithelial cells serve as a conduit for secretory antibodiesto enter the lumen and can present antigen to T cells. Theseprotective mechanisms contribute to an environment in the uterusthat is generally considered sterile, unlike the environmentin the lower female reproductive tract. The uterine environmentis in constant flux due to the concentration changes in sexhormones that occur in preparation for reproduction. The sexhormones estrogen and progesterone alter the local immune systemto prepare for conception, influence how well the immune systemwill tolerate antigenic sperm and a semi-allogeneic fetus andyet provide a network of protective immune mechanisms againstmicrobial pathogens. Understanding how sex hormones influenceuterine epithelial cell function will provide a basis for immuneprotection in the uterus.