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Chapter 34 : Site-Specific Mucosal Immunity to Fungi: Lessons Learned from Candida albicans Applied to Other Fungi
Category: Fungi and Fungal Pathogenesis
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This chapter uses Candida as the example to emphasize the uniqueness of mucosal immunity to fungi. Following a general discussion of the dogmatic host defense mechanisms against Candida albicans, a fairly detailed discussion of host defense against oral, vaginal, and gastrointestina (GI) candidiasis is reviewed to stress the uniqueness of the responses at each anatomical site and what this implies for immunity to other fungal organisms that infect multiple sites. The chapter talks about other fungi that infect multiple sites and on which studies on host defense have been focused to date, together with a road map for research on immunity to fungi that affect different mucosal tissues or anatomical sites. Historically, most studies of host defense against other medically important fungi focused on cells in the lymph nodes, spleen, or peripheral blood. Studies of host defense against the medically important fungi are certainly following the correct path and moving to evaluations at sites of infection. The authors would like this chapter to serve as an example of what the future should be relative to host defense against the medically important fungi. Development of vaccines must consider the site-specific host responses and target the site of infection with the vaccine.
Proposed immune function of the oral mucosa in HIV-positive individuals with and without OPC and <200 CD4 cells/μl. (Left) Protective mechanisms associated with the HIV-positive OPC-negative individual colonized with C. albicans when the primary defense of CD4+ T cells is below the protective threshold (200 cells/μl). The secondary defense consists of migration of CD8+ T cells to the outer epithelium and functional oral epithelial cell anti-Candida activity, which together keep Candida in check and prevent Candida infection. Th1 cytokines in saliva may also act in protection against infection, along with cytokines in tissue. (Right) Condition of OPC. In this scenario, where CD4+ T-cell numbers are below the protective threshold, CD8+ T cells are inhibited from migrating to Candida for effector function and the epithelial cells have a reduced capacity to inhibit Candida, resulting in increased susceptibility to infection. Reduced levels of Th1 cytokines in saliva may also contribute to the susceptibility. The presence of CD8+ T cells in the tissue is supported by the presence of CD8+ T-cell-associated cytokines and chemokines. Reprinted from reference 124a with permission.
Hypothesis for acquisition of symptomatic VVC. The hypothesis centers on the acquisition of VVC by achieving a threshold of Candida organisms in the vagina. Below the threshold, the vaginal presence of Candida is considered commensal and asymptomatic. Once the threshold is crossed (horizontal dotted line), the signals are initiated that allow for migration of PMNs into the vagina that cause the symptoms associated with vaginitis. Accordingly, there are different thresholds for different groups of women. For women with RVVC, the threshold is very low; it increases incrementally in women with infrequent episodes of VVC, women with no history of VVC, and adolescents. The upper limit is an arbitrary level of organism number that would be considered unattainable. Reprinted from reference 70 with permission.
Host defenses against mucosal Candida infections