Local production of chemokines during experimental vaginal candidiasis

Recurrent vulvovaginal candidiasis, caused by Candida albicans, is a signif icant problem in women of childbearing age. Although cell-mediated immunity (CMI) due to T cells and cytokines is the predominant host defense mechani sm against C. albicans at mucosal tissue sites, host defense mechanisms aga inst C albicans at the vaginal mucosa are poorly understood. Based on an es trogen-dependent murine model of vaginal candidiasis, our data suggest, tha t systemic CMI is ineffective against C. albicans vaginal infections. Thus, we have postulated that local immune mechanisms are critical for protectio n against infection. In the present study, the kinetic production of chemok ines normally associated with the chemotaxis of T cells, macrophages (RANTE S, MIP-1 alpha, MCP-1), and polymorphonuclear neutrophils (MIP-2) was exami ned following intravaginal inoculation of C. albicans in estrogen-treated o r untreated mice. Results showed significant increases in MCP-1 protein and mRNA in vaginal tissue of infected mice as early as 2 and 4 days postinocu lation, respectively, that continued through a 21-day observation period, i rrespective of estrogen status. No significant changes were observed with R ANTES, MIP-lat, or MIP-2, although relatively high constitutive levels of R ANTES mRNA and MIP-2 protein were observed. Furthermore, intravaginal immun oneutralization of MCP-1 with anti-MCP-l antibodies resulted in a significa nt increase in vaginal fungal burden early during infection, suggesting tha t MCP-1 plays some role in reducing the fungal burden during vaginal infect ion. However, the lack of changes in leukocyte profiles in vaginal lavage f luids collected from infected versus uninfected mice suggests that MCP-1 fu nctions to control vaginal C. albicans titers in a manner independent of ce llular chemotactic activity.