The identification of novel receptors involved in recognition of Mycobacterium tuberculosis

• Applicant: Georgia Schäfer, Ph.D.
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 19145300

The innate immune system is the first line of defense against microbial invasion and immediately recognizes and counters infections while the slower, more specific, adaptive response is mounted. The innate cellular response is comprised principally of phagocytic cells and is dependent on germ-line encoded receptors, the socalled ¿pattern recognition receptors (PRR)¿, which recognize conserved microbial structures. These receptors determine the type of cellular and immunological response, influencing the outcome of infection. As no concerted effort had been made to identify these molecules directly, and given their importance in the immune response to infection, a powerful generalized screening method has been established in the laboratory to identify and isolate these receptors based on their function. This technique will be applied to identify the macrophage receptors involved in the binding and recognition of Mycobacterium tuberculosis (Mtb), a facultative intracellular pathogen of macrophages and a leading cause of infectious mortality. Although very extensively studied, it has been assumed that the receptors which might play a role in mediating the entry of Mtb into macrophages can compensate for each other. Since no direct functional-based search for the macrophage receptors involved in this process has been performed, the novel screening method mentioned above will be used to screen a cDNA expression library generated from alveolar macrophages for a specific Mtb receptor. Once an Mtb-binding receptor has been identified, future studies will involve extensive molecular and functional characterization of this molecule, and its relevance to infection.

• DFG Programme: Research Fellowships
• International Connection: South Africa
• Host: Professor Dr. Gordon Brown