Although Candida albicans has the capacity for invading the deep tissues in certain immunocompromised patients, this organism rarely penetrates deeper than the dermalepidermal junction in humans with cutaneous candidiasis or when applied epicutaneously to the skin of experimental animals. Infections produced by the latter method are characterized in their early stages (one to three days after inoculation) by a prominent neutrophilic infiltrate in the epidermis, proliferation of the basal epidermal cells, and the rapid relocation of the infecting organisms to a very superficial location in the stratum corneum. There is some evidence to suggest that the neutrophils in this types of infection may function is some way other than by contacting and killing the invading Candida pseudohyphae. However, although interactions between the infecting organisms, the neutrophils, and the epidermal cells appear to result in containment of the infection to the upper epidermis, the actual mechanisms involved are poorly understood at the present time. The long-term goals of this work are to better define these mechanisms. Some of the experiments described in this proposal will be carried out using a mouse model of acute epidermal C. albicans infections, and the focus will be on early host responses to these infections in nonimmune animals. These animals will be treated to suppress the initial neutrophilic infiltrates and then in some experiments to cause redevelopment of the infiltrates using infusions of defined cell populations from syngeneic donors. The infections will be studied to determine the characteristics of the resulting cutaneous responses and whether or no the organisms have crossed the dermalepidermal junction or have been relocated to the stratum corneum. Also, the role of epidermal Langerhans cells in containing the infections to the epidermis will be studied in this model system. In addition, the possibility that Candida might directly stimulate the epidermis will be evaluate in the experimental infections and in an in vitro epidermal cell culture system. Finally, experiments will be undertaken to determine if the organisms are still viable after having been extruded from the cellular layers of the epidermis. The proposed studies should allow us to determine how the most prominent early host responses to acute cutaneous candidiasis are involved in the function of the epidermis as a barrier to deeper penetration of C. albicans pseudohyphae into the skin.
