Inability to sustain intraphagolysosomal killing ofStaphylococcus aureuspredisposes to bacterial persistence in macrophages

• DOI: 10.1111/cmi.12485
• Publication Date: 2015-08-06T13:09:44Z
• Authors: Jamil Jubrail; Paul Morris; Martin A. Bewley; Simon Stoneham; Simon A. Johnston; Simon J. Foster; Andrew A. Peden; Robert C. Read; Helen M. Marriott; David H. Dockrell
• Keywords: Phagolysosome; Intracellular parasite

Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing interrelated functions essential for bacterial clearance but rate-limiting step when macrophages challenged with large numbers major medical pathogen Staphylococcus aureus is unknown. We show that have a finite capacity intracellular fail match sustained phagocytosis microbial exposed inocula S. (Newman, SH1000 USA300 strains). ingestion by associated rapid decline viability immediately after phagocytosis. However, not all killed phagolysosome, we demonstrate reduced acidification failure phagolysosomal maturation activation cathepsin D. This results accumulation viable macrophages. engage apoptosis-associated killing. Ultittop mately undergo cell lysis, released can be internalized other cycles lysis reuptake maintain pool over time overwhelmed persistence alveolar lungs murine model.