Role of the C-type lectin receptor CLEC12A in Legionella pneumophila infection

• Applicants: Professor Dr. Bernd Lepenies; Professor Dr. Bastian Opitz
• Subject Area: Pneumology, Thoracic Surgery
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 449662545

Legionella pneumophila is an important cause of pneumonia in humans. It infects alveolar macrophages that are hijacked by the bacterium with the help of bacterial effector molecules to serve as replication niche. However, alveolar macrophages and the host are usually able to sense the infection and clear it without excessive tissue damage. The proposed project focuses on the hypothesis that C-type lectin receptors (CLRs) contribute to the regulation of the immune response against L. pneumophila. Prelimary data indicate that the CLR CLEC12A recognizes L. pneumophila, impacts the early antibacterial defense in infected macrophages in vitro positively, and down-regulates cytokine production. Based on these initial results, we aim at 1) identifying the bacterial ligand of CLEC12A; 2) investigating the impact of CLEC12A on signal transduction, intracellular defense in macrophages and L. pneumophila-induced cytokine production; 3) analyzing the role of CLEC12A in L. pneumophila pneumonia in vivo; and 4) characterizing the function of CLEC12A in human cells and samples derived from Legionnaires’ disease patients.

• DFG Programme: Research Grants