Uncovering the role of the local environment in shaping antiviral immunity of the female reproductive tract

Abstract

Abstract The female reproductive tract (FRT) is a unique barrier site. It tolerates foreign entities like sperm and the fetus for reproduction but must also be immunologically active enough to control pathogens, like viruses. Millions of women use antibiotics or anti-retrovirals, and these treatments alter the environment of the FRT by changing the microbiota or inhibiting endogenous retroviruses, but the impact of this on FRT immunity and function are understudied. Human cohort data has revealed that the vaginal microbiota profoundly influences risk of virus infection, but the mechanisms for this are not well understood. Endogenous retroviruses (ERV) are necessary for reproduction, as an ERV envelope protein is essential for placental formation, but how these elements shape immunity of the FRT is barely characterized. Preliminarily, I have found that both the microbiota and ERVs shape innate and adaptive immune cell populations and functions in the FRT. Additionally, I found that microbial derived ligands such as LPS are sufficient to induce ERV expression in the uterine epithelium. Therefore, the main hypothesis tested by my project is that the vaginal microbiota induces ERV expressionin the epithelium of the reproductive tract which in turn activates host nucleic acid sensing pathways and interferon production in the epithelium and that this response promotes local antiviral protection. Y.B. was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID; ZIAAI001115-09, ZIAAI001132-07, ZIAAI001133-08). E.S. was supported by the Training Office and OITE of the National Institute of Allergy and Infectious Diseases (Intramural AIDS Research Fellowship).