A model of human cutaneous candidosis based on reconstructed human epidermis for the light and electron microscopic study of pathogenesis and treatment

Abstract

The use of reconstructed human epidermis provided the basis for an in vitro model of human cutaneous candidosis. Candida albicans blastospores on the surface of reconstructed human epidermis provoked the following changes within 72 h: superficial keratin degradation, scaling, hyperkeratosis, parakeratosis, dyskeratosis representing hyperproliferative stress, spongiosis, and vesiculation. Great differences in the intensity of these reactions of intact reconstructed human epidermis or chemically or mechanically damaged reconstructed human epidermis illustrate the importance of the stratum corneum as a barrier. Uninfected reconstructed human epidermis showed prominent cell proliferation representing wound healing 72 h after mechanical or chemical pretreatment. These signs of repair were blocked in the presence of C. albicans and the blastospores were able to invade the stratum corneum. When desmosomes were accessible, a high affinity of C. albicans blastospores to these structures was observed. A single application of an econazole liposome dispersion decreased scaling, hyperkeratosis and dyskeratosis. Morphological alterations of C. albicans blastospores after treatment with the econazole liposome dispersion in the proposed ill vitro model were identical, as described in established animal models. This reconstructed human epidermis model of cutaneous disease may provide insight into the pathogenesis and treatment of cutaneous candidosis and may provide a substitute for animal models and investigations on humans.