Macrophage oxidative metabolism and intracellular Toxoplasma gondii.
We explored the mechanisms by which Toxoplasma gondii avoids destruction by the oxidative metabolism of normal macrophages. Unelicited murine peritoneal macrophages were infected with T. gondii and exposed to different experimental conditions. As endpoints we used measurement of hydrogen peroxide (H2O2) release and intracellular reduction of nitroblue tetrazolium dye (NBT). Three main observations were made. Firstly, different T. gondii preparations (live or dead, opsonized or not) failed to trigger the respiratory burst. Combined challenges also showed that a primary T. gondii infection was able to block H2O2 release triggered by heat-killed (HK)-Candida albicans. The H2O2 release, however, once triggered by HK-C. albicans, was not inhibited by a subsequent challenge with T. gondii. Secondly, when a respiratory burst was obtained in T. gondii-infected macrophages--for instance by stimulation with phorbol myristate acetate (PMA)--the toxic oxygen metabolites (as determined by the NBT reduction test) did not seem to reach the vacuoles containing the parasite. Thirdly, when a respiratory burst occurred in T. gondii-infected macrophages, the intracellular development of T. gondii did not seem to be affected. In conclusion, we hypothesize that T. gondii is not damaged by the macrophage oxidative metabolism because the parasite fails to encounter toxic oxygen metabolites. The killing of intracellular T. gondii, as it is commonly observed in activated macrophages, does not appear oxygen-dependent.
Chang
H R
HR
Department of Microbiology, University of Geneva Medical School, Switzerland.
Pechère
J C
JC
D000818:Animals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009580:Nitroblue Tetrazolium; D010100:Oxygen / Q000378:metabolism*; D010529:Peritoneal Cavity; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins; D014122:Toxoplasma / Q000378:metabolism*
D011994:Recombinant Proteins; D009580:Nitroblue Tetrazolium; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D010100:Oxygen