Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens.

Abstract

Normal human monocytes and activated mouse macrophages can kill or inhibit intracellular replication of Toxoplasma that are not antibody [Ab] coated whereas normal human and mouse macrophages can not. Each of these types of mononuclear phagocytes can kill Ab-coated Toxoplasma. Phagocytosis of Ab-coated Toxoplasma stimulated the respiratory burst by each of these types of mononuclear phagocytes whereas phagocytosis of organisms that were not Ab-coated stimulated the respiratory burst only by human monocytes and by activated mouse macrophages. Phagocytosis of Toxoplasma did not inhibit production of reactive O2 metabolites by normal macrophages; it failed to stimulate their production. Killing of Toxoplasma by monocytes from a child with X-linked chronic granulomatous disease and his heterozygote mother was impaired. Reactive O2 metabolites, perhaps in conjunction with lysosomal contents, may be 1st-line mechanisms whereby mononuclear phagocytes kill this organism. The exact mechanisms whereby mononuclear phagocytes inhibit the replication of those Toxoplasma that were not killed were not determined, although O2-dependent and other non-lysosomal mechanisms may be involved. The differences observed in oxidative response to phagocytosis of Toxoplasma may be one determinant of the antimicrobial activity of these cells and may account for the ability of some intracellular pathogens to survive within phagocytes. These differences may be membrane related. Studies of Toxoplasma membranes, phagocyte membrane receptors for Toxoplasma and membrane-related mechanisms for activation of the respiratory burst are needed to define their true basis.