Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens.
As previously reported, normal human monocytes (11) and activated mouse macrophages (9) are able to kill or inhibit intracellular replication of Toxoplasma that are not antibody coated, whereas normal human and mouse macrophages are not (7, 9). Each of these types of mononuclear phagocytes is able to kill antibody-coated Toxoplasma. In our studies, phagocytosis of antibody-coated Toxoplasma stimulated the respiratory burst by each of these types of mononuclear phagocytes, whereas phagocytosis of organisms that were not antibody coated stimulated the respiratory burst only by human monocytes and by activated mouse macrophages. Phagocytosis of Toxoplasma did not inhibit production of reactive oxygen metabolites by normal macrophages; rather, 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. Thus, reactive oxygen metabolites, perhaps in conjunction with lysosomal contents, appear to be first-line mechanisms whereby mononuclear phagocytes kill this organism. We were not able to determine the exact mechanisms whereby mononuclear phagocytes inhibit the replication of those Toxoplasma that were not killed, although both oxygen-dependent and other nonlysosomal mechanisms may be involved. The differences we observed in oxidative response to phagocytosis of Toxoplasma appear to 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. Further 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.
D000328:Adult; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002648:Child; D005260:Female; D005947:Glucose / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000503:physiopathology; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000469:parasitology / Q000502:physiology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000502:physiology; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010587:Phagocytosis; D014123:Toxoplasmosis / Q000469:parasitology*
D002245:Carbon Dioxide; D009580:Nitroblue Tetrazolium; D005947:Glucose; D010100:Oxygen