Both Glycolipid and Protein Components are Required for Plasmodium falciparum induced TNF-α and IL-1β Production in Human Monocytic Cells

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Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are the endogenous pyrogens which mediate fever in malaria. The excessive production of TNF-α is associated with pathology of human malaria. The nature and properties of malaria antigens, which stimulate monocyte to secrete these cytokines were studied in vitro using human monocytic cell line THP-1. THP-1 cells produced the cytokines in response to Plasmodium falciparum malaria antigens similar to the response of peripheral blood monocytes. Malaria parasite components of infected erythrocytes and their culture supernatant were separately analyzed. Soluble and insoluble components of the infected erythrocytes and their culture supernatant stimulated cytokine production by THP-1 cells. Acid, base and pronase treatments of malaria culture supernatant greatly reduced the cytokine inducing activity, suggesting that both glycolipid and protein components are essential for cell stimulation. Considering the ultrafiltration results together, we assume that a complex of glycolipid and protein stimulates host cells to induce cytokine secretion. Application of Triton X-114 solubilization and phase separation procedures to the infected erythrocytes revealed that the membrane-free hemozoin pellet did not have any stimulation activity, whereas the hydrophobic components seemed to contribute to TNF-α and IL-1β production.
長崎大学の論文