Evaluation of activated isogenic dendritic cells and imiquimod as therapeutic alternative in sporotrichosis on immunosuppressed and immunocompetent animals

Abstract

Sporotrichosis is an important mycosis with worldwide distribution that affects humans and animals. The infection is usually caused by traumatic inoculation of the fungus Sporothrix schenckii complex (composed of: S. brasiliensis, S. globosa, S mexicana and S. schenckii luriei strict sense) and clinical manifestations can range from skin infection, lymphocutaneous and systemic infection, most commonly seen in immunocompromised patients. Many cases of sporotrichosis caused by scratches from cats and by contact with contaminated wounds were reported in several cities in Brazil, mainly in Rio de Janeiro city, where the disease reached epidemic proportions and now in the state of São Paulo there are increasing reports of the incidence of disease, and is currently a major concern for health authorities. Current therapeutic tools against sporotrichosis require long periods of treatment and are associated with frequent adverse effects, sometimes severe. Therefore, there is a great need to develop more effective and safe methods for antifungal therapy, especially in immunocompromised patients. Many studies have been conducted showing the use of activated dendritic cells for the development of therapy against several disease, including tumors and chronic infections. However, studies related to this methodology in fungal infections, especially in sporotrichosis, are still scarce. The Imiquimod is an immunostimulatory compound that has been shown to be effective in the therapy against tumors and chronic infections of the skin. Moreover, it has shown microbicidal activity including antifungal, but there are no studies done to evaluate its therapeutic effect in sporotrichosis. Thus, the objective of this study is to evaluate the therapeutic capacity of isogenic activated dendritic cells and imiquimod in model of infection with S. schenckii in immunocompromised and immunocompetent mice. These data will be used in the future to generate alternative therapeutic tools against sporotrichosis. (AU)