Cell death of myeloid cells in cutaneous leishmaniasis
Protective immunity against Leishmania major is centrally orchestrated by infected myeloid cells including dendritic cells (DC) and macrophages (MF), which shape the immune response by secreting different immunoregulatory mediators. In particular, two major inflammasome-dependent cytokines, IL-1β and IL-18, have been frequently associated with the pathogenicity of Leishmania in humans and mice, and it is increasingly evident that components of the inflammasome are important for mounting protection against leishmaniasis. However, the role of myeloid cell death in immunity to Leishmania as an ultimate outcome of inflammasome activation in this process remains largely unknown.
In the present project, we aim to systematically study how L. major interferes with and impacts on cellular death processes in myeloid cells and how distinct cell death pathways affect the immune response to the parasite. By using several knockout mouse lines harbouring defects in pyroptosis, necroptosis and apoptosis, we are exploring the physiological and pathological role of specific types of myeloid cell death during the course of infection with L. major.
The knowledge obtained from these studies will substantially increase our understanding of the pathophysiology of parasite infections and will be exploited to design novel therapeutic strategies against Leishmania infection based on targeting cellular death processes.