P-selectin is a host receptor for Plasmodium MSP7 ligands

Malaria Journal

Research

S Josefin Bartholdson¹  Gavin J Wright¹  Abigail J Perrin¹ 

[1] Cell Surface Signalling Laboratory and Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridge, UK;

关键词: MSP7;    P-selectin;    Immune evasion;    Plasmodium falciparum;    Surface plasmon resonance;    MSP1;    MSRPs;    Sialyl-Lewis-X;   

DOI  :  10.1186/s12936-015-0750-z

 received in 2015-03-05, accepted in 2015-05-26,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Perrin et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.