Ficolin-1 in pediatric <i>Plasmodium falciparum</i> malaria and its possible role in parasite clearance and anemia

<i>Plasmodium falciparum</i> malaria causes significant disease, especially in young children. A successful immune response to <i>P. falciparum</i> is a major determinant of clinical outcome. The ficolins are a family of lectins that act as pattern recognition molecules and can activate the lectin complement pathway and may promote inflammation and facilitate opsonization and lysis of pathogens. Here, we have investigated the potential roles of ficolin-1 and ficolin-2 in the context of <i>P. falciparum</i> infection. We measured ficolin-1 and ficolin-2 concentrations in plasma from Malawian children presenting with uncomplicated or severe malaria or healthy controls (HCs) by ELISA. Using flow cytometry, we assessed whether ficolin-1 could bind to infected red blood cells (iRBCs) and whether it binds sialic acid on the iRBCs. Ficolin-1 and ficolin-2 plasma levels were measured in children from all clinical groups. Compared to HCs (reference), Ficolin-1 concentrations in plasma were higher in children with uncomplicated (geometric mean ratio: 1.88; 95% confidence interval [CI]: 1.25-2.82) and severe malaria (1.65; 95% CI: 1.10-2.46). Ficolin-1 levels were positively associated with peripheral blood monocyte (1.30; 1.02-1.67) and neutrophil counts (1.06; 1.00-1.13). Ficolin-2 was not associated with malaria. Hemoglobin levels were negatively associated with ficolin-1 (-0.38; -0.68 to -0.09) and ficolin-2 (-0.36; -0.68 to -0.04). Ficolin-1 bound more to iRBCs compared to uninfected RBCs, and binding was reduced in a ficolin-1 mutant that did not bind to sialic acid. These results highlight a largely overlooked role for ficolin-1 in the immune response to <i>P. falciparum</i> infection and point to a potential role for lectins contributing to parasite clearance and anaemia.