Mycobacterium leprae fails to stimulate phagocytic cell superoxide anion generation

Abstract

Mycobacterium leprae is an intracellular pathogen that is ingested by and proliferates within cells of the monocyte/macrophage series. Mechanisms by which intracellular pathogens resist destruction may involve failure to elicit a phagocyte "respiratory burst" or resistance to toxic oxygen derivatives and lysosomal enzymes. We have studied the ability of M. leprae and Mycobacterium bovis BCG to stimulate the generation of superoxide anion (02-) in vitro by human blood neutrophils and monocytes and murine peritoneal macrophages. M. Ieprae bacteria failed to stimulate significant 02-release except at high bacteria-to-cell ratios (>50:1) whether or not they were pretreated with normal serum or serum from patients with lepromatous leprosy. Either viable or irradiated BCG; on the other hand, stimulated the three cell types to release significant amounts of 02-when challenged with as few as 10 organisms per cell. Serum pretreatment enhanced the release of 02-by the three cell types. Preincubation for 18 h with viable M. Ieprae did not inhibit the ability of monocytes to respond with an oxidative burst to phagocytic stimuli. The failure of M. leprae to stimulate phagocyte 02-generation may be an important factor in its pathogenicity.

Emergence of an effective adaptive cell mediated immune response toMycobacterium lepraeis not impaired in reactive oxygen intermediate-deficient mice

“…However, M. leprae suspensions do demonstrate superoxide dismutase (Wheeler & Gregory, 1980;Thangaraj et al, 1990) and express both sodC and sodA (Williams et al, 2004). Additional indirect evidence supports a hypothesis that the ability of M. leprae to suppress the oxidative burst is a virulence factor and stems from studies at the cellular level where M. leprae or its constituents were shown to suppress host ROI production (Holzer et al, 1986;Sibley & Krahenbuhl, 1988a, b;Launois et al, 1989;Schlesinger & Horwitz, 1991) or scavenge ROI (Neill & Klebanoff, 1988;Chan et al, 1989;Vachula et al, 1989;Moura et al, 1997).…”

Helicobacter pylori induces but survives the extracellular release of oxygen radicals from professional phagocytes using its catalase activity

“…Other bacterial pathogens have evolved mechanisms to evade the oxidative response of phagocytes. For example, Toxoplasma gondii (Anderson and Remington, 1974), Yersinia pestis (Chanetzky et al, 1985), Y. enterocolitica (Lian et al, 1987), Brucella abortus (Kreutzer et al, 1979), Salmonella typhi (Kossack et al, 1981), Chlamydia trachomatis (Hammerschlag et al, 1985) and Mycobacterium leprae (Holzer et al, 1986) elicit little or no oxidative burst. In contrast, some adherent N. gonorrhoeae variants induce an enhanced oxidative burst (Knepper et al, 1997), but one that results in little release of oxidative metabolites into the extracellular milieu (Naids and Rest, 1991).…”

Susceptibility of Salmonella typhimurium and Salmonella typhi to oxygen metabolites

“…It has been demonstrated that some pathogens fail to trigger superoxide generation by macrophages [4,5,8]. We therefore examined the ability of S. typhimurium LT2, SLl102, and S. typhi 1079 to trigger hydrogen peroxide generation by murine macrophages in comparison with that of E. coli NIHJ.…”