Interferons, plasmacytoid dendritic cells and NK cells in the innate response to Leishmania parasites

• Applicant: Professor Dr. Christian Bogdan
• Subject Area: Immunology
• Term: from 2002 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5356994

The innate immunsystem plays an important role in the recognition and control of intracellular pathogens (including Leishmania [L.] major) and in the instruction of the subsequent T helper cell differentiation. Various cell types (e.g. neutrophils, macrophages, natural killer cells, and dendritic cells), cytokines (e.g. interferon-a/b, interleukin [IL]-12, IL-18) as well as the inducible nitric oxide synthase have been identified as components of the inborn defense machinery, but the signaling events that occur during the early phase of an infection in vivo are poorly understood. In this proposal, we aim to elucidate, whether reactive oxygen intermediates molecules, immunoregulators and/or signal transducers in mice infected with the protozoan parasite L. major. Furthermore, we plan to investigate to which degree the Janus kinase tyk2 (which was previously shown to be activated in various cells of the immune system by interferon-a/b, IL-3, IL-6, IL-10 and IL-12) is required for the development of a protective immune response to L. major. To this end, the course of infection will be monitored in wild-type, NADPH oxidase- or tyk2-deficient mice and the activation and functional capacity of granulocytes, natural killer cells, macrophages, dendritic cells and T cells will be analysed.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1110: Innate Immunity