Oxygen-dependent microbicidal systems of phagocytes and host defense against intracellular protozoa

Abstract

The role of oxygen-dependent microbicidal systems of leukocytes in the host defense against the major nonerythrocytic intracellular protozoa which infect man--Toxoplasma gondii, Trypanosoma cruzi, and the Leishmania species--is reviewed. The hydrogen peroxide-halide-peroxidase microbicidal system is uniformly cidal to these organisms in vitro. Peroxidase-independent oxygen product(s) toxicity is more variable. Studies to data indicate that phagocytes which contain granule peroxidase and which have the capacity to generate a vigorous respiratory burst; eg, neutrophils and monocytes, possess substantial activity against these protozoa. The absence of granule peroxidase together with the markedly attenuated respiratory burst of resident macrophages leaves these cells with a severe microbicidal defect. These protozoa can enter resident macrophages in the absence of antibody and survive and replicate within the intracellular environment. Enhancement of the antiparasite activity of resident macrophages can be accomplished either by activation of these cells by exposure to sensitized T-cell products, or by the introduction of exogenous peroxidase into the vacuole. Other factors influencing the ability of protozoa to survive intracellularly include the capacity of these organisms to avoid effective triggering of the macrophage respiratory burst and the levels of endogenous scavengers of oxygen products within the parasite.