Modulation of C-type lectin receptor expression by helminth: setting the threshold for sensing of mycobacteria?

• Applicant: Professor Dr. Roland Lang
• Subject Area: Immunology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405489036

C-type lectin receptors (CLR) of the DECTIN2 family sense cell wall glycolipids of pathogenic mycobacteria (e.g. M. tuberculosis and M. leprae). Expression of these CLR is down-regulated by IL-4/IL-13, which are typical for the immune response to helminth infection. Epidemiological evidence suggests that underlying worm infections can increase the risk to become infected and to develop active tuberculosis. Building on our established Ethiopian-German collaboration, we propose to investigate whether helminth-infection down-regulates CLR expression in healthy, in latently infected and in individuals with active tuberculosis, as well as in leprosy patients with tuberculoid vs. lepromatous disease. The impact of helminth infection on Th response and its association with CLR expression will be determined in these cohorts. We will also search for association of genetic variants in CLR loci with susceptibility to infection with MTB and to develop active TB using genotyping by SNP microarray. Finally, mechanisms of IL-4-dependent and -independent indirect, and of direct, regulation of CLR expression and function by helminths will be explored using patient samples ex vivo and in genetically defined mouse models.

• DFG Programme: Research Grants
• International Connection: Ethiopia
• International Co-Applicant: Markos Abebe Alemayehu, Ph.D.