Characterization of myeloid suppressor cell activity in experimental leishmaniasis

• Applicant: Professor Dr. Uwe Ritter
• Subject Area: Immunology
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 188763720

In experimental leishmaniasis, the clinical course of disease depends on the genetically determined ability of the infected mouse strain to mount a protective T cell-mediated immune response. C57BL/6 mice control parasite replication, whereas BALB/c mice develop a chronic course of disease. Considering these divergent phenotypes, it is most likely that parameters regulating the adaptive immune response against L. major parasites differ in C57BL/6 and BALB/c mice. Recently, myeloid suppressor cells have been described to suppress T cell functions. The most potent suppressive cells are inflammatory CD11b+ monocytes (IMC) that are characterized by the expression of high levels of lymphocyte antigen 6 complex C (Ly-6C), but are negative for Ly-6G. We quantified IMCs at the site of infection and skin-draining lymph nodes (SDLNs) of infected C57BL/6 and BALB/c mice. BALB/c mice showed an increase of IMC at the site of infection and SDLNs, whereas the numbers of IMCs in C57BL/6 SDLNs were not affected. Thus, we propose the hypothesis that IMCs migrate to the site of infection and SDLNs of BALB/c mice to suppress the development of an efficient T cell response. The overall goal of this project is to characterize the different T cell-suppressing mechanisms mediated by IMCs in the experimental model of leishmaniasis.

• DFG Programme: Research Grants