Abstract
BackgroundPlasmodium 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.MethodsTo 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.ResultsPlasmodium 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-LewisX.ConclusionsNovel 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0750-z) contains supplementary material, which is available to authorized users.
Highlights
Plasmodium parasites typically elicit a non-sterile but protective immune response in human host populations, suggesting that the parasites actively modulate normal immunological mechanisms
‘bait’ proteins, in this case P-selectin and controls, are arrayed in microtitre plates and probed with enzyme-tagged ‘preys’, in this case merozoite ligands, which have been purposefully clustered into pentamers thereby increasing overall binding avidity to detect even the most fleeting of interactions
One simple and informative validation criteria for interactions detected using the AVidity-based EXtracellular protein Interaction Screening (AVEXIS) approach is to ask whether the interaction is dependent on the bait-prey orientation [22]
Summary
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. Plasmodium parasites have evolved effective immunoregulatory mechanisms so that sterile immunity develops very slowly, if at all, and is rapidly lost in areas of lower transmission [4]. P-selectin (SELP, known as CD62P) is a host cell surface receptor protein that is known to influence malaria-associated pathology, both in human patients and rodent infection models [5,6,7,8]. P-selectin is required for the efficient recruitment of circulating leukocytes to sites of localized inflammation, being rapidly up-regulated on the surface of inflamed vascular endothelial cells [9, 10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
