CD14 hi CD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so

摘要: With more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for effective anti-malaria vaccine. Limited details on the mechanisms protective immunity are a barrier to vaccine development. Antibodies play important role in malaria monocytes key effectors antibody-mediated protection phagocytosing antibody-opsonised infected erythrocytes (IE). Eliciting antibodies that enhance phagocytosis IE is therefore potential component vaccine, requiring robust assays determine ability elicited stimulate this vivo. The which ingest nature do so unknown. Purified trophozoite-stage P. falciparum were stained ethidium bromide, opsonised anti-erythrocyte incubated fresh whole blood. Phagocytosis TNF production individual monocyte subsets was measured flow cytometry. Ingestion confirmed imaging CD14hiCD16+ phagocytosed produced efficiently CD14hiCD16- CD14loCD16+ monocytes. Blocking experiments showed Fcγ receptor IIIa (CD16) but not IIa (CD32a) or I (CD64) necessary phagocytosis. ingested when peripheral blood mononuclear cells reconstituted autologous serum heat-inactivated serum. Antibody-opsonised rapidly complement C3 (t1/2 = 2-3 minutes) inhibited dose-dependent manner inhibitor activation, compstatin. Compared other subsets, expressed highest levels 4 (CD11c) activated 3 (CD11b) subunits. We show special TNF. While ingestion mediated IIIa, sufficient allow phagocytosis; despite opsonisation antibody, also required opsonisation. Assays measure vaccines elicit antibody response should consider their promote fix complement.