Identification and characterization of mast cell functions in Sporothrix schenckii infections

• Applicant: Professor Dr. Marcus Maurer
• Subject Area: Dermatology
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 242029477

In recent years, the incidence of invasive fungal infections has increased dramatically both in Europe and in China. One of the reasons for this is the growing population of immunocompromised patients. Current treatment options are not sufficient and the mortality of invasive fungal infections remains unacceptably high. To change this, we need to better characterize the pathogenesis of severe fungal infections. On this basis we can develop novel and better treatment options.Mast cells (MCs) express several crucial receptors and mediators in antifungal responses. The host defence responses to fungal pathogens share many features of MC-driven immune responses against bacteria and parasites. We, therefore, hypothesize that MCs play an important role in host defence responses against fungi and that MC-targeted interventions can help to improve the protection from and resolution of fungal infections. To test this hypothesis, we will establish a fungal infection mouse model using Sporothrix schenkii (Spor) as a prototype pathogen for fungi. Spor commonly causes infections of the skin in immunocompetent individuals but severe invasive infections in immunocompromised patients. Specifically, we will assess and compare Spor-infections both clinically and by histopathologic analyses in MC-deficient mice and their normal wild type littermates. Next, we will assess mast cell responses to Spor by analysing degranulation, cytokine release, proliferation and migration, and we will determine the effects of mast cells and their products on Spor survival and pathogenicity. Finally, we want to investigate the relevance of mast cells for inducing Th1 CD4 cell responses by analysing migration and activation of dendritic cells (DCs) which has been shown to be crucial in Spor-Infection. This project will help to better characterize the role of MCs in host defence reactions against fungal infections. More importantly, our project could help to provide better tools and novel therapeutic options for the treatment of patients infected with Spor and other fungal pathogens.

• DFG Programme: Research Grants
• International Connection: China
• Participating Person: Professor Dr. Zuotao Zhao, Ph.D.