Dataset Information

Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa

ABSTRACT: Duffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and Plasmodium knowlesi merozoites. By contrast, Plasmodium falciparum parasites, which are the dominant cause of malaria in West and Central Africa, use multiple RBC receptors for invasion. Whether DARC is one of these receptors has never been systematically explored. We used flow cytometry and microscopy-based approaches to investigate whether P. falciparum parasites preferentially invade specific Duffy RBC phenotypes and explored two potential explanations for invasion preference – differences in RBC membrane biophysical properties and surface protein composition – using flickering spectroscopy and mass spectrometry. P. falciparum parasites showed a consistent preference for Duffy-positive RBCs, and some biophysical properties and membrane proteins varied between Duffy-positive and Duffy-negative RBCs. We then used our in vitro invasion data to parametrise an evolutionary-epidemiological model of the relationship between P. falciparum and the allele responsible for Duffy negativity (FYBES). Our model accounts for immunity against P. falciparum virulence, gained through exposure, and thus mutations that impede infection are not always advantageous. The inhibition of P. falciparum invasion that we observed in vitro leads to FYBES frequencies increasing at low levels of P. falciparum transmission but decreasing at high levels of P. falciparum transmission. The impact of P. falciparum on the prevalence of Duffy negativity may therefore be most apparent in lower P. falciparum transmission settings. Our findings reveal a link between Duffy negativity and P. falciparum for the first time and suggest that the DARC receptor may be directly or indirectly involved in P. falciparum invasion of human RBCs which could, together with P. vivax, explain the distribution of Duffy negativity in sub-Saharan Africa.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Malaria

SUBMITTER: Robin Antrobus

LAB HEAD: Professor Julian C. Rayner

PROVIDER: PXD065766 | Pride | 2026-03-02

REPOSITORIES: Pride

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			Action	DRS
	JR_BM_DUFFY2_16_7ul_220622.xlsx	Xlsx
	JR_BM_DUFFY2_16_7ul_220622_run1.raw	Raw

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Publications

Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa.

Manneh Balanding B Introini Viola V Reed James J Rotariu Madalina M Antrobus Robin R Cicuta Pietro P Weekes Michael P MP Penman Bridget S BS Rayner Julian C JC

Molecular biology and evolution 20260203

Duffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and Plasmodium knowlesi parasites. By contrast, Plasmodium falciparum parasites use multiple RBC receptors for invasion. Whether DARC is one of these receptors has never been systematically explored. We used flow cytometry and microscopy-based approaches to investigate whether P. falciparum parasites preferentially invade specific Duffy RBC phenotypes and explo ...[more]

PMID: 41634932

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