Project Details
Projekt
The phagosomal fate of Mycobacterium tuberculosis-infected dying/dead cells
Applicant
Professor Dr. Ulrich E. Schaible
Subject Area
Parasitology and Biology of Tropical Infectious Disease Pathogens
Term
from 2011 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 198133502
Macrophages are the predominant cells clearing up dying/dead cells. This process is essential in tissue remodelling during inflammation and healing with removal of massive aggregates of dying neutrophils in infectious foci as prime example. Mycobacterium tuberculosis and Salmonella typhimurium are facultative intracellular pathogens with a phagosomal life style. Both bacteria induce host cell death during infection. Dying/dead cells are usually engulfed by phagocytes called efferocytes and subsequently transported to lysosomes for membrane and macromolecule degradation and recycling. Uptake of necrotic but not apoptotic cells is accompanied by cell activation. However, when cells succumb to cell death due to infection with intracellular bacteria, their intracellular fate is expected to be different. We will analyse the intracellular fate of bacteria-infected dying/dead cells in efferocytes, characterize the respective phagosomes, identify efferocyte and bacteria associated molecules determining the biogenesis of those phagosomes, and study whether the pathogens benefit from entering novel host cells enwrapped in dying/dead cells. We hypothesize that bacteria and/or their compounds alter the fate of apoptotic/necrotic material within the phagosomal pathway, i.e. either promoting or inhibiting degradation. Delineating the intracellular fate of dying/dead cells upon bacterial infection will provide novel insights into phagosome biogenesis in inflamed infection sites and the function of infected cell degradation for survival or elimination of intracellular bacteria.
DFG Programme
Priority Programmes
