Role of the C-type lectin receptors SIGNR3, MICL and DCIR in the recognition of plasmodial ligands and their contribution to the pathogenesis of cerebral malaria

• Applicant: Professor Dr. Bernd Lepenies
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437392749

Malaria is a major global cause of death from infectious diseases, resulting in more than 200 million clinical cases and more than 600.000 deaths per year. A fatal complication is cerebral malaria that causes neurological symptoms in affected patients. The infection of susceptible mouse strains with Plasmodium berghei ANKA (PbA) is currently the model of choice to study the pathogenesis of cerebral malaria. Whereas the role of adaptive immunity in the development of cerebral malaria has been analyzed quite in detail, little is known about the contribution of innate immunity to cerebral malaria induction. To date, most studies have focused on the role of Toll-like receptors in this process. In contrast, almost no studies have investigated whether and how C-type lectin receptors (CLRs) affect the course of malaria. CLRs belong to a family of lectins that recognize carbohydrate structures on pathogens such as viruses, bacteria, fungi, and parasites, thus they are involved in the initiation of immune responses. In own preliminary work, it was shown that CLRs contribute to Plasmodium recognition and may indeed play essential roles in cerebral malaria development. In the first part of the proposed project, distinct plasmodial ligands of the CLR SIGNR3 will be identified and characterized biochemically. In the second part, mechanistic studies will reveal how the CLRs SIGNR3, MICL, and DCIR impact the course of cerebral malaria. In addition to PbA infection of CLR-deficient mouse lines, mixed bone marrow chimeras will be generated to analyze the function of these CLRs in the pathogenesis of cerebral malaria.

• DFG Programme: Research Grants