Duffy Antigen Expression in Erythroid Bone Marrow Precursor Cells of Genotypically Duffy Negative Individuals
| Autor: | Niraj H. Tolia, Lenore L. Carias, Edwin Chen, Peter A. Zimmerman, Célia Dechavanne, Roeper B, Krishnan S, Woost Pg, Christopher L. King, Rich Fong, Ghosh A, Yves Colin, James W. Jacobberger, Nichole D. Salinas, Bennett S, Metral S, Sebastien Dechavanne, Benoit Gamain |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
biology Plasmodium vivax biology.organism_classification Virology Phenotype 03 medical and health sciences Red blood cell 0302 clinical medicine medicine.anatomical_structure Antigen 030220 oncology & carcinogenesis Genotype parasitic diseases medicine biology.protein Bone marrow Antibody Erythroid Precursor Cells 030304 developmental biology |
| DOI: | 10.1101/508481 |
| Popis: | The gene encoding the Duffy blood group protein (Fy, CD234; additional designations Duffy Antigen Receptor of Chemokines [DARC] and Atypical Chemokine Receptor 1 [ACKR1]) is characterized by a SNP in a GATA-1 transcription factor binding site associated with the erythrocyte silent (ES) phenotype.FYEShomozygous people are viewed to be highly resistant to blood stage infection withPlasmodium vivax. Increasingly, however, studies are reportingP. vivaxinfections in Fy-negative individuals across malarious African countries whereFYESapproaches genetic fixation. This suggests thatP. vivaxhas evolved a Fy-independent RBC invasion pathway, or that the GATA-1 SNP does not abolish Fy expression. Here, we tested the second hypothesis through binding studies to erythroid lineage cells using recombinantP. vivaxDuffy binding protein, the parasite’s invasion ligand and Fy6-specific antibodies. We first observed variable Fy expression on circulating RBCs, irrespective ofFYgenotype;FYESRBCs were periodically Fy-positive. Furthermore, during thein vitroerythroid differentiation of CD34+ cells and onex vivobone marrow samples, we observed Fy expression on erythroid precursor cells fromFYESpeople. Finally, the Fy6-specific nanobody, CA111 was used to capture Fy from the surface ofFYESRBCs. Our findings reveal that the GATA-1 SNP does not fully abolish Fy expression and provide insight on potential susceptibility of Fy-negative people to vivax malaria.SignificanceDuffy blood group negativity results from a single nucleotide polymorphism (SNP) in the gene promoter, and reaches genetic fixation in many African ethnicities. Because the Duffy protein (Fy) is an important contact point duringPlasmodium vivaxhuman red blood cell invasion, Fy-negativity is considered to confer resistance toP. vivaxmalaria. With recent studies in African countries reportingP. vivaxinfection in Fy-negative people, we studied Fy expression across erythroid development. Here we report that theFYpromoter SNP does not abolish Fy protein expression in erythroid progenitors developing in the bone marrow. These results further emphasizes the importance of reticulocytes as targets forP. vivaxblood stage infection and propose a mechanism forP. vivaxinfections in Fy-negative people. |
| Databáze: | OpenAIRE |
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