Role of adaptive immunity in the pathogenesis of Candida albicans keratitis

Purpose: Innate immunity had been thought to be critical in the pathogenesis and prognosis of fungal keratitis. This study was conducted to determine whether experimental Candida albicans keratitis (CaK) induces an adaptive immune response. Methods: Experimental murine CaK was induced by intrastromal injection of C. albicans spores, and fungal pneumonia was induced by intranasal inhalation of spores. Active immunization was accomplished by subcutaneous injection of heat-inactivated spores. Serum was collected at different times after the induction of primary or secondary CaK for the measurement of IgA, IgG, IL-4, and IFN-γ. Immunohistochemistry was used to detect immunoglobulin deposition and lymphocyte infiltration in diseased corneas. Results: After intrastromal injection of C. albicans spores in immunocompetent mice, typical CaK occurred, and the corneas healed in 3 weeks. When recovered corneas were challenged again with spores, they developed milder CaK and healed faster than with primary CaK. Mice that had recovered from pulmonary infection or had been immunized also showed increased resistance to CaK. Compared with naive mice, the mice that had previously encountered C. albicans produced more IgG and IgA in serum and more immunoglobulin deposition and lymphocyte infiltration in corneas on secondary CaK induction. Cytokines assays showed that the immune response induced by CaK was biased toward the T-helper (Th)1 type. Conclusions: Th1-type adaptive immune response and immunologic memory were induced by C. albicans keratitis, and previous contact with Candida preparation enhanced the resistance of the host to subsequent corneal challenge with the same fungus. Active immunization might be an effective strategy to prevent fungal keratitis in populations at high risk.