Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes.

PLoS Pathogens
Jens E V PetersenSteve M Taylor

Abstract

Sickle-trait hemoglobin protects against severe Plasmodium falciparum malaria. Severe malaria is governed in part by the expression of the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that are encoded by var genes, specifically those variants that bind Endothelial Protein C Receptor (EPCR). In this study, we investigate the effect of sickle-trait on parasite var gene expression and function in vitro and in field-collected parasites. We mapped var gene reads generated from RNA sequencing in parasite cultures in normal and sickle-cell trait blood throughout the asexual lifecycle. We investigated sickle-trait effect on PfEMP1 interactions with host receptors CD36 and EPCR using static adhesion assays and flow cytometry. Var expression in vivo was compared by assembling var domains sequenced from total RNA in parasites infecting Malian children with HbAA and HbAS. Sickle-trait did not alter the abundance or type of var gene transcripts in vitro, nor the abundance of overall transcripts or of var functional domains in vivo. In adhesion assays using recombinant host receptors, sickle-trait reduced adhesion by 73-86% to CD36 and 83% to EPCR. Similarly, sickle-trait reduced the surface expression of EPCR-binding PfEMP1...Continue Reading

References

May 1, 1997·Transactions of the Royal Society of Tropical Medicine and Hygiene·S L CranmerB M Cooke
Jan 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Rushina CholeraRick M Fairhurst
Sep 24, 2010·PLoS Computational Biology·Thomas S RaskThomas Lavstsen
Apr 26, 2011·The American Journal of Pathology·Katerina Dorovini-ZisTerrie E Taylor
Mar 27, 2012·The Lancet Infectious Diseases·Steve M TaylorRick M Fairhurst
May 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Thomas LavstsenThor G Theander
May 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marion AvrilJoseph D Smith
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jul 17, 2013·Journal of Thrombosis and Haemostasis : JTH·E A M BouwensL O Mosnier
Sep 6, 2014·Frontiers in Cellular and Infection Microbiology·Danny A MilnerTerrie E Taylor
Dec 22, 2015·The Lancet. Haematology·Tatiana M Lopera-MesaRick M Fairhurst
Jun 30, 2016·EMBO Molecular Medicine·Jakob S JespersenThomas Lavstsen
Sep 27, 2016·Nature Communications·Fu-Lien HsiehMatthew K Higgins
May 11, 2017·Malaria Journal·Casper HempelTrine Staalsø
Jun 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Natasha M ArcherManoj T Duraisingh

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.