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Published on: December 4, 2015
Unveiling P. vivax invasion pathways in Duffy-negative individuals
Isabelle Bouyssou1, Sara El Hoss2, Cécile Doderer-Lang3
1Malaria Genetics and Resistance Unit, INSERM U1201, Institut Pasteur, Université Paris Cité, 75015 Paris, France; École Doctorale ED515 "Complexité du Vivant", Sorbonne Université, 75005 Paris, France; Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Université Paris Cité, 75015 Paris, France.
Vivax malaria can infect Duffy-negative individuals in sub-Saharan Africa. Plasmodium vivax merozoites invade erythroblasts expressing the Duffy antigen receptor for chemokines (DARC) during development, revealing a hidden infection reservoir.
Area of Science:
- Malariology
- Cell Biology
- Immunology
Background:
- Vivax malaria is considered absent in sub-Saharan Africa due to widespread Duffy antigen receptor for chemokines (DARC) deficiency.
- The Duffy-binding protein (PvDBP) interaction with DARC is the established pathway for Plasmodium vivax merozoite invasion of reticulocytes.
- Recent vivax malaria cases in Duffy-negative individuals challenge the current understanding of Plasmodium vivax invasion mechanisms.
Purpose of the Study:
- To investigate the potential invasion pathways of Plasmodium vivax in Duffy-negative individuals.
- To determine if Duffy-negative erythroblasts express DARC during erythroid differentiation.
- To assess the susceptibility of DARC-expressing erythroblasts to Plasmodium vivax merozoite invasion.
Main Methods:
- Analysis of DARC expression during terminal erythroid differentiation in Duffy-negative erythroblasts.
- In vitro invasion assays using Plasmodium vivax merozoites and DARC-positive Duffy-negative erythroblasts.
- Genotypic analysis of Duffy-negative individuals with reported vivax malaria cases.
Main Results:
- A subset of Duffy-negative erythroblasts transiently expresses DARC during terminal erythroid differentiation.
- Plasmodium vivax merozoites, regardless of origin, successfully invaded DARC-positive Duffy-negative erythroblasts.
- Duffy-negative individuals may harbor silent, deep Plasmodium vivax infections at erythropoiesis sites.
Conclusions:
- Plasmodium vivax can invade Duffy-negative individuals by targeting DARC-expressing erythroblasts.
- Duffy-negative populations in sub-Saharan Africa may represent a significant, underestimated reservoir for vivax malaria.
- This finding has potential clinical implications for malaria control and diagnosis in the region.
