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

Asier Garcia-Senosiain,Morten Hanefeld Dziegiel,Michael Theisen,Ikhlaq Hussain Kana,Bright Adu,Sanne Hertegonne,Subhash Singh,Manoj Kumar Das

doi:10.1038/s42003-021-02511-5

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.

Highlights

Antibody-mediated opsonic phagocytosis (OP) of Plasmodium falciparum blood-stage merozoites has been associated with protection against malaria
Neutrophils are the major cell types involved in IgG-mediated phagocytosis of P. falciparum blood-stage merozoites
We found that both the neutrophils and monocytes were active in the phagocytosis of merozoites, neutrophils were more active despite the antibody type (i.e., IP or NIP) used to opsonize merozoites (Fig. 1b)

Summary

Introduction

Antibody-mediated opsonic phagocytosis (OP) of Plasmodium falciparum blood-stage merozoites has been associated with protection against malaria. Engagement of FcγRs triggers potent immune cell mechanisms resulting in the release of soluble factors[11] and/or phagocytosis[12,13,14] leading to parasite killing Of these mechanisms, the opsonic phagocytosis (OP)[12,13,14] has by far been the most consistent correlate of protection against malaria in sero-epidemiological studies. Using an in vitro phagocytosis assay, which included all peripheral blood leukocytes (PBL) (in proportion to their normal composition in peripheral blood), we investigated the role of different cell types and their respective FcγRs in IgG-mediated phagocytosis of blood-stage P. falciparum merozoites. Using the phagocytosis assay we tested the association between IgG-mediated OP of blood-stage P. falciparum merozoites and protection against febrile malaria in two different longitudinal cohort studies performed in Ghana and India

Methods

Results

Conclusion