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

• Applicant: Professor Dr. Roland Lang
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405489036

Tuberculosis (TB) and helminth infections are coexisting and highly prevalent in many African countries. Epidemiology links helminth infections with higher susceptibility to develop latent or active TB, but the underlying mechanisms are poorly understood. C-type lectin receptors (CLR) are important innate pattern recognition receptors for sensing of microbial carbohydrate and glycolipid ligands. Several CLR bind mycobacterial ligands and contribute to the immune response during infection with Mycobacterium tuberculosis (MTB). CLR of the Dectin-2 family are induced by exposure to microbial ligands, including mycobacterial cord factor and the BCG vaccine. On the other hand, the Th2 cytokine interleukin (IL)-4 inhibits their expression in macrophages and down-regulates cytokine production in response to mycobacteria. Since helminths induce type 2 immunity with high levels of IL-4, we hypothesize that Dectin-2 family CLR may be down-regulated in worm-infected patients. Africa also carries a high burden of HIV infection, which is associated with higher prevalence of helminth-infection and increased risk to develop TB. HIV is bound by several CLR, but how HIV infection regulates CLR expression is unknown. In this German-African cooperation project of partners from Ethiopia, Nigeria and Germany, we propose to investigate whether expression levels and sensing function of CLR involved in recognition of MTB are indeed affected by underlying helminth- or HIV-infection.

• DFG Programme: Research Grants
• International Connection: Ethiopia, Nigeria
• Major Instrumentation: flow cytometer
• Instrumentation Group: 3500 Zellzähl- und Klassiergeräte (außer Blutanalyse), Koloniezähler
• International Co-Applicants: Markos Abebe Alemayehu, Ph.D.; Dr. Bartholomew Ibeh