Mucosal cellular immune mechanisms, including those in the urogenital tract, are poorly understood. In the past, studies of urogenital mucosal immunity concentrated on humoral mechanisms, which did little to increase our understanding of immunity against microbial invasion. Recently, it has become apparent that effectors of cell-mediated immunity (CMI) are present in the lower genital tract, including T cells in the vagina, which are phenotypically distinct from those in the peripheral circulation. These data support the proposed role of CMI in protection against urogenital pathogens such as Chlamydia trachomatis and Candida species. Furthermore, the high frequency of vulvovaginal candidiasis (VVC) in immunocompromised patients emphasizes the potential importance of CMI in mucosal Candida infections. Recurrent vulvovaginal candidiasis (RVVC) is a unique form of VVC which affects up to 5% of otherwise healthy women. We have access to a large population of women with RVVC and have established a well-defined animal model of experimental vaginal candidiasis. Studies to date indicate that recurrent vaginal infections in women with RVVC occur despite the presence of normal peripheral CMI reactivity to Candida and that Candida-specific CMI pre-induced in the periphery of mice does not protect from experimental vaginal candidiasis. Thus, based on our results we predict that CMI host defense mechanisms other than those expressed in the periphery are important at the vaginal mucosa. We hypothesize that cellular immunity expressed in the vaginal mucosa represents a localized host defense mechanism against Candida. To test this hypothesis, we will focus on the characterization of T cell subpopulations localized in the vaginal mucosa of mice and determine how they change and respond to Candida following a vaginal infection. Results will be compared to peripheral lymphoid cells. Results of these studies will identify cell populations expressed locally in the female genital tract that may be important for vaginal resistance to candidiasis and provide insight into local host defense against other urogenital pathogens.
|Pereira, H Anne; Tsyshevskaya-Hoover, Irina; Hinsley, Heather et al. (2010) Candidacidal activity of synthetic peptides based on the antimicrobial domain of the neutrophil-derived protein, CAP37. Med Mycol 48:263-72|