GM‐CSF‐induced priming of human neutrophils for enhanced phagocytosis and killing of asexual blood stages of Plasmodium falciparum: synergistic effects of GM‐CSF and TNF

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Abstract
Granulocyte macrophage‐colony stimulation factor (GM‐CSF), which is a haematopoietic cytokine generated by activated T lymphocytes and macrophages during infection, was investigated for its effects on human neutrophil‐mediated killing of asexual blood forms of Plasmodium falciparum. Pretreatment of neutrophils with human recombinant‐GM‐CSF markedly increased the parasite killing (measured by a radiometric assay), in the presence of normal serum (containing complement), immune serum (IS), purified IgG (from IS) or heat inactivated IS. GM‐CSF pretreatment also enhanced phagocytosis of the parasite by neutrophils and the expression of CR3, FcγRII and FcγRIII receptors. Treatment of neutrophils with a combination of GM‐CSF and TNF resulted in a synergistic increase in phagocytosis and killing of the parasite. The findings suggest that GM‐CSF is likely to form part of the cytokine network responsible for regulating the antiparasitic activity of the neutrophil in malaria.

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