# Ficolin-1 in pediatric Plasmodium falciparum malaria and its possible role in parasite clearance and anemia

## TL;DR

This study explores how ficolin-1, a part of the immune system, may help fight malaria in children and contribute to anemia.

## Contribution

The study reveals a new role for ficolin-1 in the immune response to malaria and its potential involvement in parasite clearance and anemia.

## Key findings

- Ficolin-1 levels are elevated in children with uncomplicated and severe malaria compared to healthy controls.
- Ficolin-1 binds to infected red blood cells, and this binding is reduced in a mutant that cannot bind sialic acid.
- Higher ficolin-1 levels are associated with increased monocyte and neutrophil counts and lower hemoglobin levels.

## Abstract

Plasmodium falciparum malaria causes significant disease, especially in young children. A successful immune response to P. falciparum 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 P. falciparum 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 P. falciparum infection and point to a potential role for lectins contributing to parasite clearance and anaemia.