title: Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes.
abstract: Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL to the membrane of P. falciparum-infected erythrocytes, which could be inhibited by mannose, was observed. Further characterization revealed that MBL reacted with a P. falciparum glycoprotein identical to the 78-kDa glucose-regulated stress protein of P. falciparum. MBL seems to be a disease modifier in clinical malaria and to function as an opsonin for erythrocytes invaded by P. falciparum and may thus be involved in sequestration of the parasite, which in turn may explain the association between homozygosity for MBL variant alleles and high parasite counts.
authors.affiliation: Tissue Typing Laboratory-7631, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark. Garred@post5.tele.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.forename: Jørgen A L
authors.initials: JA
authors.lastname: Kurtzhals
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Malhotra
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Bamenla Q
authors.initials: BQ
authors.lastname: Goka
authors.forename: Bartholomew D
authors.initials: BD
authors.lastname: Akanmori
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Lars
authors.initials: L
authors.lastname: Hviid
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D014644:Genetic Variation; D005838:Genotype; D005869:Ghana; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008024:Ligands; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000276:immunology
chemical_list: D008024:Ligands; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D009895:Opsonin Proteins