Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Increased level of CD16/Fc{gamma}RIIIA on CD14+CD16+ monocytes of children with severe Plasmodium falciparum anemia compared to children with cerebral or uncomplicated malaria.

Abstract

Fc gamma receptor IIIA (CD16/FcgammaRIIIA) on monocytes/macrophages may play an important role in the pathogenesis of severe malarial anemia (SMA) by promoting phagocytosis of IgG-coated uninfected red cells and by allowing the production of TNF-alpha upon cross-linking by immune complexes (ICs). However, not much is known about the differential expression of this receptor on monocytes of children with severe malaria and uncomplicated malaria. Therefore, we investigated the expression of CD16/FcgammaRIIIA on monocytes of children with SMA, cerebral malaria (CM), and their age-matched uncomplicated malaria controls by flow cytometry. Since CD14low (CD14(+)) monocytes are considered more mature and macrophage-like than CD14high (CD14(++)) monocytes, we also compared the level of expression of CD16/FcgammaRIIIA according to CD14 level and studied the relationship between CD16/FcgammaRIIIA expression and intracellular TNF-alpha production upon stimulation by ICs. CD16/FcgammaRIIIA expression was the highest overall on CD14(+)CD16(+) monocytes of children with SMA at enrollment. At convalescence, SMA children were the only ones to show a significant decline in the same parameter. By contrast, there were no significant differences among groups in the expression of CD16/FcgammaRIIIA on CD14(++)CD16(+) monocytes. A greater percentage of CD14(+)CD16(+) monocytes produced TNF-alpha upon stimulation than any other monocyte subset and the amount of intracellular TNF-alpha correlated positively with CD16/FcgammaRIIIA expression. Furthermore, there was an inverse correlation between hemoglobin levels and CD16/FcgammaRIIIA expression in children with SMA and their controls. These data suggest that monocytes of children with SMA respond differently to P. falciparum infection by overexpressing CD16/FcgammaRIIIA as they mature which could enhance erythrophagocytosis and TNF-alpha production.