Neutrophils dominate in opsonic phagocytosis of P. falciparum blood-stage merozoites and protect against febrile malaria

Abstract

Antibody-mediated opsonic phagocytosis (OP) of Plasmodium falciparum blood-stage merozoites has been associated with protection against malaria. However, the precise contribution of different peripheral blood phagocytes in the OP mechanism remains unknown. Here, we developed an in vitro OP assay using peripheral blood leukocytes that allowed us to quantify the contribution of each phagocytic cell type in the OP of merozoites. We found that CD14 + +CD16− monocytes were the dominant phagocytic cells at very low antibody levels and Fc gamma receptor (FcγR) IIA plays a key role. At higher antibody levels however, neutrophils were the main phagocytes in the OP of merozoites with FcγRIIIB acting synergistically with FcγRIIA in the process. We found that OP activity by neutrophils was strongly associated with protection against febrile malaria in longitudinal cohort studies performed in Ghana and India. Our results demonstrate that peripheral blood neutrophils are the main phagocytes of P. falciparum blood-stage merozoites.

Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children

“…Further, antibodies promoted activation of NK cells, which occurs via engagement of FcγRIIIa, which may also contribute to immunity against sporozoites [18, 23]. Our data, and other published data [23, 43] suggest that neutrophils are substantially more active in phagocytosis than monocytes and are much more abundant than monocytes in blood (45–70% and 2–10% of peripheral blood white blood cells, respectively). This suggests neutrophils may play a more prominent role in clearance of sporozoites in blood.…”

Asymptomatic carriage ofPlasmodium falciparumin children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio

“…Although IgG levels were comparable between individuals with asymptomatic and symptomatic parasitemia, plasma from individuals in the younger group with asymptomatic parasitemia significantly inhibited parasite invasion in vitro compared to plasma from those with symptomatic malaria, in younger age group. Given that the parasitemia levels between asymptomatic and symptomatic individuals in this group were similar, this data may reflect the fact that antibodies control iRBCs through several mechanisms apart from invasion blocking such as facilitating opsonic phagocytosis by phagocytes by neutrophils (62). If such other metrics are similar between the 2 groups then invasion blocking effects may be hidden by the cumulative action of circulating antibodies.…”

Neutrophils in malaria: The good, the bad or the ugly?

“…Furthermore, merozoite phagocytosis was shown in vitro to be enhanced in the presence of immune sera or when interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α) or granulocyte‐monocyte colony‐stimulating factor (GM‐CSF) was added 13,47,48 . Recently, it was demonstrated that at low levels of specific antibodies, merozoites are mainly phagocytosed by monocytes through FcγRIIA, whereas at high antibody levels, neutrophils are more effective through synergistic action of FcγRIIA and FcγRIIIB 49 …”

“…13,47,48 Recently, it was demonstrated that at low levels of specific antibodies, merozoites are mainly phagocytosed by monocytes through FcγRIIA, whereas at high antibody levels, neutrophils are more effective through synergistic action of FcγRIIA and FcγRIIIB. 49 This may suggest that monocytes are mainly responsible for the phagocytosis of parasites in non-immune patients, while neutrophils appear more important in immune patients. As an illustration, the presence of trophozoites, gametocytes, schizonts and haemozoin within the neutrophils and a large number of neutrophils with phagocytosed merozoites were described in a recent clinical case report.…”