T cell response during Group B Streptococcus vaginal colonization and ascending infection

Abstract

Abstract Pre-term birth, miscarriage, and other adverse pregnancy outcomes remain the primary cause of neonatal death and are associated with bacterial ascending infections within the female reproductive tract. Group B Streptococcus (GBS), a vaginal tract colonizer, is a leading contributor to adverse pregnancy outcomes and neonatal invasive disease. We have developed a mouse model of GBS vaginal colonization and ascending infection and have observed increased IL-17 production in mice that cleared GBS colonization compared to those still colonized. Thus, we hypothesize that IL-17 and IL-17-producing cells may be important for host defense; yet, the immune dynamics during GBS vaginal persistence and ascending infection/adverse pregnancy outcomes remain unknown. T cells are a major source of IL-17 in the mucosa. To assess the role of adaptive immunity during GBS colonization, we colonized RAG1+/+ and RAG1−/− mice with GBS and observed increased persistence of GBS in the vaginal tract of the RAG1−/− mice. To determine the cellular source of IL-17 within the reproductive tract of GBS-colonized mice, we isolated immune cells from vaginal, cervical, and uterine tissues at the time of GBS clearance and performed flow cytometry. TCRɣδ+ cells comprised the highest percentage of RORɣT+ immune cells in the vagina, cervix, and uterus. We further observed an increased percentage of TCRɣδ+ cells in the uterus of GBS-colonized mice compared to naïve mice at day 9 post-inoculation, at which point half the mice had cleared. We hypothesize that IL-17-producing TCRɣδ+ cells contribute to GBS clearance in the murine reproductive tract. Future studies will assess GBS vaginal persistence and ascending infection in IL-17- and TCRɣδ-deficient mouse lines.