Journal Article

P-selectin is a host receptor for Plasmodium MSP7 ligands

Bartholdson, S Josefin, Perrin, Abigail J, Wright, Gavin J

2015

Overview

Background Plasmodium parasites typically elicit a non-sterile but protective immune response in human host populations, suggesting that the parasites actively modulate normal immunological mechanisms. P-selectin is a cell surface receptor expressed in mammals, that is a known component of the inflammatory response against pathogens and has been previously identified as a host factor that influences malaria-associated pathology both in human patients and rodent infection models. Methods To better understand the molecular mechanisms underlying the involvement of P-selectin in the pathogenesis of malaria, a systematic extracellular protein interaction screen was used to identify Plasmodium falciparum merozoite surface protein 7 (MSP7) as a binding partner of human P-selectin. This interaction, and those occurring between P-selectin and Plasmodium MSP7 homologues, was characterized biochemically. Results Plasmodium falciparum MSP7 and P-selectin were shown to bind each other directly via the N-terminus of PfMSP7 and the P-selectin C-type lectin and EGF-like domains. Orthologous proteins in the murine parasite Plasmodium berghei (PbMSRP1 and PbMSRP2) and mouse P-selectin also interacted. Finally, P-selectin, when complexed with MSP7, could no longer bind to its endogenous carbohydrate ligand, Sialyl-Lewis X . Conclusions Novel interactions were identified between Plasmodium MSP7 protein family members and host P-selectin receptors. Since PfMSP7 could prevent interactions between P-selectin and its leukocyte ligands, these results provide a possible mechanism for the known immunomodulatory effects of both MSP7 and P-selectin in malaria infection models.

• Publisher: BioMed Central,BioMed Central Ltd
• Subject: Animals / Biomedical and Life Sciences / Biomedicine / Control / Drug therapy / Entomology / Health aspects / Humans / Immune response / Infectious Diseases / Lectins / Lectins, C-Type - metabolism / Ligands / Malaria / Membrane Proteins - genetics / Membrane Proteins - metabolism / Mice / Microbiology / Oligosaccharides - metabolism / P-Selectin - genetics / P-Selectin - metabolism / Parasitology / Plasmodium falciparum / Plasmodium falciparum - genetics / Plasmodium falciparum - metabolism / Protozoan Proteins - genetics / Protozoan Proteins - metabolism / Public Health / Sialyl Lewis X Antigen / Tropical Medicine