Leishmanicidal mechanisms of human polymorphonuclear phagocytes

Area of Science:

• Immunology
• Cell Biology
• Parasitology

Background:

• Leishmania donovani is an intracellular parasite causing visceral leishmaniasis.
• Phagocytes play a crucial role in controlling parasitic infections.
• Understanding the interaction between phagocytes and Leishmania is key to developing treatments.

Purpose of the Study:

• To investigate the mechanisms by which human phagocytes kill Leishmania donovani.
• To compare the phagocytic and leishmanicidal efficiencies of different human phagocyte types.
• To elucidate the role of the myeloperoxidase system in Leishmania killing.

Main Methods:

• In vitro infection of human peripheral blood phagocytes (neutrophils, monocytes, eosinophils) with Leishmania donovani amastigotes.
• Light and electron microscopy for ultrastructural analysis.
• Ultrastructural cytochemistry for lysosomal enzymes and hydrogen peroxide (H2O2).
• Assay for parasite killing and subsequent promastigote emergence.
• Testing phagocytes from patients with chronic granulomatous disease.

Main Results:

• Neutrophils exhibited the highest phagocytic efficiency, followed by monocytes and then eosinophils.
• Amastigotes were degraded by neutrophils but survived within monocytes.
• Lysosome-phagosome fusion and H2O2 production were observed in all infected phagocyte types.
• Neutrophils demonstrated significant leishmanicidal activity, dependent on the myeloperoxidase-H2O2-halide system.
• Phagocytes from chronic granulomatous disease patients showed reduced killing capacity.

Conclusions:

• Human neutrophils possess potent leishmanicidal mechanisms involving the myeloperoxidase-H2O2-halide system and respiratory burst products.
• Monocytes' limited microbicidal activity contributes to Leishmania survival within these cells.
• Targeting these microbicidal pathways could offer therapeutic strategies against leishmaniasis.