Mechanisms involved in elimination of organisms from experimental cutaneous Candida albicans infections in guinea pigs

Abstract

Experimental cutaneous Candida albicans infections were produced in guinea pigs either by using occlusive dressings over the organisms or by applying them to the shaved skin directly without occlusive dressings. In either model there was clearance of the infecting organisms from the skin by a process involving profuse scaling of the keratinized layer in which they were confined. However, for each type of infection the mechanisms producing this scaling seemed to involve different parts of the host defense system. Infections produced under occlusive dressings were characterized by a rapid accumulation of polymorphonuclear leukocytes (PMN) in the epidermis and formation of thick crusts in which organisms were trapped. Sloughing of the crust removed the organisms. In this model, evolution of the lesions and the rate of clearance of the organisms did not depend on prior immunity to Candida. Two possible mechanisms for attraction of PMN into the lesions were direct activation of the alternative complement pathway by the organisms in the lesions and direct chemotactic activity in components of Candida albicans. In contrast, infections produced without occlusive dressings showed only minimal epidermal PMN infiltration, but also underwent profuse scaling of the keratinized layer. This response appeared to depend on cell-mediated immunity. Only animals with previously-acquired delayed hypersensitivity to Candida antigens could undergo this type of scaling, and indeed, this response was transferable to nonimmue animals with peritoneal exudate cells from Candida-immune animals. Clearance of the infecting organisms from this type of infection was significantly faster in immune than in nonimmune animals. It is postulated that a lymphokine released from lymphocytes in the upper epidermis acts on epidermal cells to increase the rate of keratin turnover either by the mitotic rate of the germinal cells or by increasing their rate of keratinization.