Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40

Abstract

Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus , group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli , and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus , group A and B streptococci, Escherichia coli , Neisseria gonorrhoeae , and Candida albicans . We have previously shown that staphylococcal and streptococcal superantigens induce inflammatory chemokines from vaginal epithelial cells through the immune costimulatory molecule CD40 through use of a CRISPR cas9 knockout mutant and complemented epithelial cell line. In this study, we show that the potential vaginal pathogens S. aureus , group A and B streptococci, E. coli , an Enterococcus faecalis strain, and C. albicans in part use CD40 to stimulate interleukin-8 (IL-8) production from human vaginal epithelial cells. In contrast, N. gonorrhoeae does not appear to use CD40 to signal IL-8 production. Normal flora Lactobacillus crispatus and an Enterococcus faecalis strain that produces reutericyclin do not induce IL-8. These data indicate that many potential pathogens, but no normal commensals, induce IL-8 to help disrupt the human vaginal epithelial barrier through CD40, thus providing a potential therapeutic target for drug development. IMPORTANCE Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus , group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli , and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. In contrast, Neisseria gonorrhoeae does not use CD40 to stimulate interleukin-8. Normal flora lactobacilli and at least one E. faecalis strain do not induce interleukin-8.