Effect of immunosuppression on epidermal defenses in a murine model of cutaneous candidiasis

A number of pharmacologic treatment regimens were used to evaluate the early defenses against experimental cutaneous candidiasis in nonimmune mice. Severe immunosuppression of the animals was found to have little effect on the numbers of Candida pseudohyphae that initially infected the skin, but it did, however, modify the progression of the infection afterwards. Of the regimens tested, only the combination of intraperitoneal cyclophosphamide and intravenous phorbol myristate acetate both completely eliminated the epidermal neutrophilic infiltrates characteristic of these infections and promoted a significant degree of Candida invasion into the dermis. However, the epidermal proliferative response to the infections, generally considered to be an important mechanism of defense against superficial mycoses, was equivalent at the sites of both invasive and noninvasive foci, and it was generally comparable to that in normal animals. Dermal invasion in the treated animals was also found to occur at a time (between 12 and 24 hours after inoculation) when the epidermis was maximally proliferating. In contrast to these results, the intraperitoneal administration of colchicine significantly suppressed epidermal proliferation at the Candida foci but had only minimal effects in promoting dermal invasion. Therefore, whereas epidermal proliferation could be involved in the eventual clearance of these experimental cutaneous Candida infections, this mechanism apparently has little to do with either limiting the number of organisms initially infecting the skin or preventing their invasion into the dermis.