Linking early IL-4 producing cell types with allergic pulmonary inflammation induced by infection with Cryptococcus neoformans

• Applicant: Privatdozent Dr. Uwe Müller
• Subject Area: Immunology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 172924446

Cryptococcus neoformans, is an opportunistic fungal pathogen that has been identified as a causative agent of fatal pulmonary and cerebral inflammation in immunocompromised patients. We have recently shown the key roles of IL-4, IL-13, IL-4Rα in driving allergic pulmonary inflammation associated with production of IgE, induction of alternatively activated macrophages, and pulmonary disorders, e.g. enhanced mucus production and hyperreactivity of the bronchi. Because innate IL-4 production by eosinophils and/or basophils shaping adaptive IgE responses have been shown in parasite infection models, we are interested to study innate IL-4 production in fungal allergic bronchopulmonary mycosis induced by C. neoformans. This is a unique model demonstrating a gene-dosage effect of the IL-4Rα allele which directs the level of IgE being produced in a dose-dependent manner. The project aims at clarifying (1) which innate cells (eosinophils, basophils or others) produce early IL-4, (2) the time point at which a T helper 2 (Th2) cell response is established in the pulmonary lymph nodes and lung tissue, (3) whether innate or adaptive IL-4 production is associated with alternative macrophage activation, and (4) whether the resulting IgE response has an effector function or is merely a disease parameter useful for monitoring.

• DFG Programme: Research Grants