Description
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterium that colonizes the cervicovaginal tract in 20-30% of healthy women. Colonization is asymptomatic, however during pregnancy, GBS can cause serious complications such as chorioamnionitis and urinary tract infections. More severely, GBS can also be vertically transmitted to the newborn causing pneumonia, sepsis or meningitis. Current prophylaxis, consisting of late gestation screening and intrapartum antibiotics, have failed to entirely prevent transmission and GBS remains the leading cause of bacterial neonatal meningitis in the United States. However, little is known about the specific interactions between GBS and epithelial cells of the female reproductive tract and the role of the human immune system during GBS colonization. Gaining insight into factors controlling vaginal colonization is essential for developing novel therapeutics to limit maternal GBS carriage and prevent transmission to the vulnerable newborn. Using human vaginal and cervical cell lines and our established mouse model of vaginal GBS colonization, I have begun to characterize key host factors that impact vaginal colonization. In vitro, I have observed increased transcript and protein levels of cytokines and chemokines involved in innate and adaptive immunity, such as IL-1_, IL-6, IL-36_, IL-8 and CCL20, after challenge with different GBS strains. A specific GBS strain, CJB111, has been identified to exhibit prolonged persistence in the murine vaginal tract compared to other lab strains of GBS. Interestingly, I have demonstrated that the CJB111 strain adheres to and invades cervical cells more readily than other strains, suggesting that certain GBS strains could use cervical cells as a reservoir to establish long-term colonization. I further hypothesized that prolonged persistence might provoke more robust immune responses. Correspondingly, we have investigated engagement of adaptive immunity during colonization and found increased IL-17 production in mice colonized with CJB111 compared to other GBS strains. Further, addition of exogenous IL-17 accelerated clearance of CJB111. We conclude that both host immune responses and bacterial strain differences are crucial in modulating GBS vaginal colonization
