Proteases in myeloid cells control inflammatory processes, activate adaptive immunity and remodelled tissues during infection. Macrophages phagocytose mycobacteria and restrict phagosomal maturation and thereby bacterial access to lysosomal proteases. In addition to intracellular, endolysosomal protease pool, phagocytes also release proteases during activation and cell lysis. In tuberculosis, intra- and extracellular proteolysis could be influenced by the hypoxia which is a feature of tuberculous granulomas. Our studies aim to understand how hypoxia influences proteolysis in phagocytes and subsequent inflammatory responses. The GRK-PRO consortium employs cutting-edge proteomic, genetic, biochemical and bioengineering techniques to identify the range of substrates of proteases and distinguish between physiological and pathological proteolysis.

Project participants from FLI:

Prof. Dr. Anca Dorhoi
Shah Faisal
Abhishek Sharma