Immunity to Candida.

Abstract

Candida species are commensal fungal organisms as well as opportunistic pathogens of mucosal tissues. From the commensal relationship, most healthy individuals have demonstrable Candida-specific immunity. In immunocompromised persons, however, fungal infections caused primarily by C. albicans often occur. In HIV disease, up to 90% of HIV+ persons will have a symptomatic episode of oropharyngeal candidiasis (OPC) sometime during progression to AIDS, many of which become recurrent. In contrast, vulvovaginal candidiasis (VVC) and systemic Candida infections (candidaemia) are much less common during HIV disease, indicating the diversity and compartmentalization of the host response to Candida. Both innate resistance and acquired immunity play some role in maintaining C. albicans in the commensal state and protecting the systemic circulation. Polymorphonuclear leukocytes (PMNL) are critical for protection against systemic infections, whereas cell-mediated immunity (CMI) by Th1-type CD4+ T-cells is important for protection against mucosal infections. However, there is a discordant role for CMI at the vaginal versus oral mucosa, whereas little to no role for local or systemic CMI is evident at the vaginal mucosa. In contrast, there is a strong correlation between reduced blood CD4+ cells and the incidence of OPC, but it remains unclear whether systemic or local CMI is more important. Evaluation of systemic CMI in a cohort of HIV+ individuals with and without mucosal candidiasis revealed that Candida-specific CMI is not different between HIV+ persons with OPC or VVC and HIV- persons. Thus, the correlation of reduced CD4+ cell numbers to OPC may be explained by the requirement for a threshold number of systemic CD4+ cells to protect the oral mucosa together with the status of local immunity. Indeed, HIV+ persons with and without OPC had a Th2-type salivary cytokine profile suggestive of susceptibility to Candida infection compared with a protective Th0/Th1-type profile in HIV- persons. Candida-specific antibodies, although present, are controversial relative to a role in protection or eradication of infection. While studies of mucosal innate resistance are limited, we recently found that epithelial cells from saliva and vaginal lavages of healthy individuals inhibit the growth of Candida in vitro. This epithelial cell anti-Candida activity requires cell contact by viable cells with no role for soluble factors, including saliva. Interestingly, oral epithelial cells from HIV+ persons with OPC had significantly reduced activity, indicating some protective role for the epithelial cells. Taken together, these data suggest that immunity to Candida is site-specific, compartmentalized and involves innate and/or acquired mechanisms from systemic and/or local sources.