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: Peter Garred, Morten A Nielsen, Jørgen A L Kurtzhals, Rajneesh Malhotra, Hans O Madsen, Bamenla Q Goka, Bartholomew D Akanmori, Robert B Sim, Lars Hviid
• Journal: Infection and immunity (Infect Immun) Vol. 71 Issue 9 Pg. 5245-53 (Sep 2003) ISSN: 0019-9567 [Print] United States
• PMID: 12933871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• MBL2 protein, human
• Mannose-Binding Lectin
• Opsonin Proteins

Topics

• Adolescent
• Alleles
• Amino Acid Sequence
• Animals
• Case-Control Studies
• Child
• Child, Preschool
• Erythrocytes (immunology, parasitology)
• Genetic Variation
• Genotype
• Ghana
• Humans
• In Vitro Techniques
• Infant
• Infant, Newborn
• Ligands
• Malaria, Falciparum (genetics, immunology, parasitology)
• Mannose-Binding Lectin (analogs & derivatives, genetics, immunology, metabolism)
• Molecular Sequence Data
• Opsonin Proteins (genetics, metabolism)
• Plasmodium falciparum (immunology)