Immune Activation in the Female Reproductive Tract After Colonization with Group B Streptococcus

Streptococcus agalactiae (group B streptococcus, GBS) is a Gram-positive bacterium found in the female rectovaginal tract capable of being transmitted to newborns and causing life-threatening disease. Little is known about the specific bacterial factors that promote GBS colonization and persistence in the cervicovaginal tract. One GBS virulence factor regulated by the two-component regulatory system CovR/CovS is the B-hemolysin/cytolysin (B-H/C) toxin, encoded by the cylE gene. Research in our laboratory has investigated the role of this regulatory system in vaginal niche establishment. We have performed global transcriptional profiling of vaginal epithelium during association with wild-type GBS, as well as mutant strains deficient in CovR and B-H/C, in order to characterize the host response during GBS colonization. Results of microarray analysis and quantitative real-time PCR show that infection with the CovR-deficient mutant increased induction of pro-inflammatory cytokines and chemokines compared to that observed with the cylE mutant or wild-type GBS strains. These results suggest that the B-H/C toxin is the principal provocative factor for vaginal cell immune activation. We are currently investigating the role of the B-H/C toxin in the immune activation of the cervix. Finally, we will further explore immune activation in the female reproductive tract by testing wild-type and mutant GBS strains in vivo. Continued studies will clarify how GBS modulates the host interaction, which is crucial in elucidating its switch from a normal vaginal inhabitant to an invasive pathogen.