Inhibition of Ca2+ Signaling by Mycobacterium tuberculosisIs Associated with Reduced Phagosome–Lysosome Fusion and Increased Survival within Human Macrophages

Signaling by Mycobacterium tuberculosis Is Associated with Reduced Phagosome–Lysosome Fusion and Increased Survival within Human Macrophages

Complement receptor (CR)-mediated phagocytosis of Mycobacterium tuberculosis by macrophages results in intracellular survival, suggesting that M . tuberculosis interferes with macrophage microbicidal mechanisms. As increases in cytosolic Ca 2 1 concentration ([Ca 2 1 ] c ) promote phagocyte antimicrobial responses, we hypothesized that CR phagocytosis of M . tuberculosis is accompanied by alter...

Phagosome-lysosome fusion is a calcium-independent event in macrophages

Phagosome-lysosome membrane fusion is a highly regulated event that is essential for intracellular killing of microorganisms. Functionally, it represents a form of polarized regulated secretion, which is classically dependent on increases in intracellular ionized calcium ([Ca2+]i). Indeed, increases in [Ca2+]i are essential for phagosome-granule (lysosome) fusion in neutrophils and for lysosoma...

Macrophages and Intracellular Survival in Human Inhibition of Phagosome-Lysosome Fusion Signal Transduction: Contribution to Exhibit Altered Calmodulin-Dependent Phagosomes Mycobacterium tuberculosis

ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X(7)-dependent process inducing bacterial death by phagosome-lysosome fusion.

Mycobacterium tuberculosis survives within host macrophages by actively inhibiting phagosome fusion with lysosomes. Treatment of infected macrophages with ATP induces both cell apoptosis and rapid killing of intracellular mycobacteria. The following studies were undertaken to characterize the effector pathway(s) involved. Macrophages were obtained from p47(phox) and inducible NO synthase gene-d...

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway

BACKGROUND Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persis...