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. Author manuscript; available in PMC: 2013 Apr 1.
Published in final edited form as: Cytokine. 2011 Dec 17;58(1):118–128. doi: 10.1016/j.cyto.2011.11.021

Figure 2.

Figure 2

Schematic diagrams representing the mechanism for the effects of vaginal S100 alarmins on PMN migration during VVC. (A) Epithelial cell sensitivity – organism threshold hypothesis. In women with no history of VVC (left panel), their vaginal epithelial cells are insensitive to Candida. These women remain asymptomatic as even in the presence of high numbers for Candida (threshold number to initiate pathological response rarely breached). In women with RVVC (right panel), vaginal epithelial cells are extremely sensitive to Candida. These women are susceptible to symptomatic infection following exposure to even small numbers of Candida (low organism threshold). The thresholds represent an arbitrary organism number of the upper limit for vaginal fungal burden that would initiate symptomatic infection. (B) Consequences of epithelial cell sensitivity. Under asymptomatic condition (left panel), vaginal epithelial cells are insensitive to Candida and remain unstimulated following interaction with Candida. In turn, PMN migration does not occur in the absence of S100 alarmin production. Strong cell-surface Annexin A1-dependent (proposed based on oral epithelial cells) antifungal activity provides non-inflammatory means to maintain Candida at the commensal state. Under symptomatic conditions (right panel), vaginal epithelial cells are extremely sensitive to Candida and exert weak antifungal activity through Annexin A1. Epithelial cells become activated upon recognition of Candida via unidentified PRRs. S100 alarmins are secreted as danger signals toward which vaginal PMNs migrate through vaginal epithelium. Once in the vaginal epithelium, recruited PMNs also produce S100 alarmins as part of positive feedback mechanism to further amplify the PMN response. (C) S100 alarmin response in immunopathogenesis. PMN infiltration remains minimal in the absence of S100 alarmin production by vaginal epithelial cells, therefore, no symptom occurs (left panel). In contrast, high concentrations of S100 alarmins in vaginal epithelium trigger PMN migration to the vaginal cavity, resulting in pathological inflammation associated with the symptoms of infection. The inflammatory process enhances Candida growth and hyphal formation (right panel).