Adhesion of Plasmodium Falciparwn‐lnfected Erythroeytes to Human Cells and Seeretion of Cytokines (IL‐1‐β, IL‐1RA, IL‐6, IL‐8, IL‐10, TGFβ, TNFα, G‐CSF, GM‐CSF)

Abstract

The scientific interest in tbe pbysical interaction of Plasmodium falciparum-infected erytbrocytes with host cells stems from the suggestion ibat excessive binding in the microvasculature leads to severe malaria. Tbe authors studied, therefore, two parasites for their ability to adbere to normal human cells and to induce cytokine production, one parasite lacking a binding capacity (DD2) and one which adhered to CD36⁺ transfected CHO cells (MCAMP). The MCAMP parasites readily bound to platelets and erytbrocytes and to monocytes, polymorphonuclear granulocytes and EBV-transformed B cells as seen by ligbt and electron microscopy. Platelets were frequently attached in large numbers to the infected erythrocyte surface and groups of infected erytbrocytes were sometimes held together by several platelets. Nine out of 17 cytokines tested were found to be secreted into the culture supernatants after 35 h of co-eultures containing monocytes or unfractionated peripheral blood mononuclear cells (PBMC) and parasites (IL-lRA, IL-6, IL-8, IL-10, TGFβ, TNFα, G-CSF, IL-1-β, and GM-CSF). Three additional cytokines were also present in low levels (<200pg/ml, IL-2, IL-4, IFNγ) in tbe culture supernatants after incubation of the cells for 4 days. TNFa, IL-RA, and IL-8 were secreted from polymorphonuclear granulocytes, LGLs and T cells. Platelets and, to a lesser degree, monocytes and T cells secreted large amounts of TGFβ (10–30 ng/ml). Cytokines may participate in tbe patbogenesis but also the suppression of immune responses seen during acute malarial infections.