Abstract Background Fc gamma receptor III b (FcγRIIIb), a glycosylphosphatidylinositol (GPI) linked receptor, is the most abundant neutrophil FcγR on neutrophils followed by FcγRIIa. FcγRs interact with IgG and studies have reported the association of antibody dependent neutrophil phagocytosis (ADNP) with protection against malaria, but the role of specific FcγRs is not clear. Methods To investigate the relative importance of FcγRIIIb and FcγRIIa as mediators of ADNP of Plasmodium falciparum infected erythrocytes (IEs), purified neutrophils from healthy donors were treated with tumor necrosis factor (TNF) to mobilize the intracellular stores of FcγRIIIb to the surface followed by enzymatic cleavage of GPI-linked FcγRIIIb with phosphatidylinositol phospholipase C (PIPLC). Results In TNF/PIPLC treated neutrophils, detectable FcγRIII decreased by 79% (relative gMFI = 21 ± 4.5), while FcγRIIa detection increased by 82% (relative gMFI = 182 ± 2.3), compared to untreated neutrophils (relative gMFI = 100%). When opsonised IEs were incubated with TNF/PIPLC treated neutrophils, ADNP by FcγRIIIb-depleted neutrophils increased significantly (relative phagocytosis = 585% ± 108%) compared to untreated neutrophils (relative phagocytosis = 100%, p = 0.042). Using FcγR blocking we show that compared to no-blocker (relative phagocytosis = 100%), ADNP was reduced more than five-fold by FcγRIIa blocker alone (relative phagocytosis ∼17% ± 1.5%, p0.05) and to a similar extent by combined FcγRIIa and FcγRIII blockers (relative phagocytosis ∼24% ± 5.5%, p 0.05). Conclusions Our data suggest that FcγRIIa is the main phagocytic receptor that mediates ADNP of IEs and that FcγRIIIb acts as a decoy receptor.
Saeed et al. (Tue,) studied this question.