Evidence for activation of a respiratory burst in the interaction of human neutrophils with Mycobacterium tuberculosis

Abstract

We examined the capacity of human neutrophils to develop a respiratory burst, as monitored by superoxide release, in response to interaction with Mycobacterium tuberculosis. Serum-opsonized, heat-killed mycobacteria induced significant release of superoxide from neutrophils after 30 min of exposure, with a maximum release of 34 ± 1.7 nmol/30 min per 5 x 106 neutrophils occurring with a mycobacterium/neutrophil ratio of 40:1. Similar levels of superoxide release were induced by live mycobacteria. Neutrophil superoxide production was reduced significantly with exposure to unopsonized organisms or by substitution of heat-inactivated serum for opsonization. Mycobacterial components including culture filtrate, purified protein derivative, and the cell wall polysaccharide arabinogalactan failed to induce significant release of superoxide from neutrophils. Transmission electron microscopy demonstrated that more than 90% of the neutrophils had ingested heat-killed mycobacteria concomitant with the development of respiratory burst activity. These data suggest that the presumed failure of neutrophil killing of mycobacteria cannot be attributed to a lack of phagocytosis or respiratory burst activation.

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

“…tuberculosis does not successfully parasitize human neutrophils, and several studies have demonstrated that PMNs kill intracellular M . tuberculosis by both oxygen-dependent and -independent mechanisms 606162. Finally, caution is required in comparing Ca 2+ -mediated signal transduction of neutrophils with that of macrophages, as these two classes of phagocytes have been reported to differ in the Ca 2+ dependence of antimicrobial functions 2659.…”

Streptococcus pyogenes bacteria modulate membrane traffic in human neutrophils and selectively inhibit azurophilic granule fusion with phagosomes

“…The molecular mechanism(s) that allows S. pyogenes to escape intracellular killing by human phagocytes remains undefined, but the fusion of granules with the phagosome could be a target for such a mechanism. Phagosome-lysosome fusion has long been regarded as one of the crucial steps in the bactericidal responses of human phagocytes, and an inhibition of this process has been described for a number of pathogenic bacteria such as Mycobacterium tuberculosis (Armstrong and Hart, 1971;Goren et al ., 1976;May and Spagnuolo, 1987;Russell, 2001), Legionella pneumophilia (Horwitz, 1983;Swanson and Isberg, 1995;Tilney et al ., 2001), Brucella abortus (Frenchick et al ., 1985;Arenas et al ., 2000;Celli and Gorvel, 2004) and Bordetella pertussis (Steed et al ., 1992). Some pathogenic microorganisms modulate their intracellular habitat in other ways in order to survive and proliferate inside phagocytes.…”

Membrane retrieval in neutrophils during phagocytosis: inhibition by M protein-expressingS. pyogenesbacteria

“…Furthermore, adding to the complexity, many pathogens are able to modulate the phagosomal maturation sequence. This can occur through an inhibition of phagosome-lysosome fusion as has been described for a number of pathogenic bacteria such as Mycobacterium tuberculosis [16,17], Legionella pneumophilia [18], Brucella abortus [19], and Bordetella pertussis [20].…”