Deciphering lyso-metabolic communication strategies during infection
Phagolysosomes are primary organelle system to sense and kill many invading pathogens. Beyond this the lysosome has recently emerged as a dynamic and central metabolic hub. It recycles nutrients from digested material, can regulate metabolic signaling nodes (e.g. mTOR) and engage in extensive direct or indirect interactions with other membrane-bound organelles. This includes stable physical junctions with other membrane compartment, which likely provide direct routes for the exchange of lipids, ions and other metabolic signals.
Current work in the lab is focused on untangling how direct and indirect lysosomal communication controls macrophage functions during inflammation and infection. We are further investigating how defects in lysosomal functions contribute to immunological disorders. Of particular interest is hereby the lysosome-linked Chediak-Higashi syndrome, a primary immunodeficiency, whose patients suffer from recurring bacterial infections and a, causally unresolved, secondary hyper-inflammatory phase.
Phago-lysosomes engulfing pathogens alter their interactions with other organelles
Cyan: Candida albicans; blue: lysosomes, yellow: mitochondria
Lysosomes in macrophages engage direct- and indirect organelle communications upon bacterial infection
Left image – yellow: lysosome; red: mitochondria; Right movie – green: Transcriptionfactor EB