Sex hormone modulation of human uterine epithelial cell immune responses

Sexually transmitted infections are a major worldwide public health 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 little discomfort to death. The female reproductive tract has evolved innate and adaptive immune mechanisms that protect from microbial infection, thereby reducing infection and disease. Central to this protection are the epithelial cells that line the female reproductive tract. In the uterus, columnar epithelial cells provide a physical barrier to microbial infection, possess toll-like receptors that detect pathogens and secrete a number of constitutive and induced factors that directly or indirectly hinder infection. For example, uterine epithelial cells secrete peptides that destroy pathogenic microbes. In addition, epithelial cells produce chemokines and cytokines that attract and activate innate immune cells and serve as a link to the adaptive immune system. Further, uterine epithelial cells serve as a conduit for secretory antibodies to enter the lumen and can present antigen to T cells. These protective mechanisms contribute to an environment in the uterus that is generally considered sterile, unlike the environment in the lower female reproductive tract. The uterine environment is in constant flux due to the concentration changes in sex hormones that occur in preparation for reproduction. The sex hormones estrogen and progesterone alter the local immune system to prepare for conception, influence how well the immune system will tolerate antigenic sperm and a semi-allogeneic fetus and yet provide a network of protective immune mechanisms against microbial pathogens. Understanding how sex hormones influence uterine epithelial cell function will provide a basis for immune protection in the uterus.