The Role Of Adaptive Immunity In The Pathogenesis Of Fungal Keratitis

PURPOSE.Innate immunity had been thought to be critical in pathogenesis and prognosis of fungal keratitis(FK).This study was to determine whether experimental FK induces an adaptive immune response.METHODS.Experimental murine FK was induced by intrastromal injection of Candida albicans spores,and fungal pneumonia was induced by intranasal inhalation of spores. Active immunization was done by subcutaneous injection of heat-inactivated spores. Serum was collected at different times after induction of primary or secondary FK for measurement of IgA,IgG,IL4 and IFNγ.Immunohistochemistry was utilized to detect immunoglobulin deposition and lymphocyte infiltration in diseased corneas.RESULTS.After intrastromal injection of Candida albieans spores in immunocompetent mice,typical FK occurred,and the corneas healed in three weeks.When recovered corneas were challenged again with spores,they developed milder FK and healed faster compared with primary FK.Mice that had recovered from pulmonary infection or had been immunized also showed increased resistance to FK.Compared to naive mice,the mice that had previously encountered Candida albicans produced more IgG and IgA in serum and more immunoglobulin deposition and lymphocyte infiltration in corneas upon secondary FK induction.Cytokines assays showed that the immune response induced by FK was biased toward Th1 type.CONCLUSIONS.A Th1-type adaptive immune response and immunological memory were induced by fungal keratitis,and previous contact with fungal preparation enhanced the resistance of the host to subsequent corneal challenge with the same fungus.Active immunization might be an effective strategy to prevent FK in high risk populations.