Unveiling P. vivax invasion pathways in Duffy-negative individuals

Isabelle Bouyssou (1, 2, 3) , Sara El Hoss (4) , Cécile Doderer-Lang (5) , Matthieu Schoenhals (6) , Lova Tsikiniaina Rasoloharimanana (6) , Inès Vigan-Womas (7) , Arsène Ratsimbasoa (8) , Andargie Abate (9) , Lemu Golassa (9) , Solenne Mabilotte (5) , Pascal Kessler (10) , Micheline Guillotte-Blisnick (3) , Francisco J Martinez (3) , Chetan E Chitnis (3) , John Strouboulis (4) , Didier Ménard (1, 3, 5, 11)

1 Génétique du paludisme et résistance - Malaria Genetics and Resistance
2 ED515 - Ecole Doctorale Complexité du Vivant
3 Biologie de Plasmodium et Vaccins - Malaria Parasite Biology and Vaccines
4 King‘s College London
5 DIHP - Dynamique des interactions hôte pathogène
6 Institut Pasteur de Madagascar
7 Institut Pasteur de Dakar
8 Université de Fianarantsoa
9 AAU - Addis Ababa University
10 CRBS - Centre de Recherche en Biomédecine de Strasbourg
11 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]

Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underesti- mated biological problem with potential clinical consequences in sub-Saharan Africa.

Keywords: malaria; Plasmodium vivax; Duffy antigen receptor for chemokines; Duffy-negativity; Sub-Saharan Africa; erythropoiesis; invasion pathways

Domains: Life Sciences [q-bio]

Isabelle Bouyssou, Sara El Hoss, Cécile Doderer-Lang, Matthieu Schoenhals, Lova Tsikiniaina Rasoloharimanana, et al.. Unveiling P. vivax invasion pathways in Duffy-negative individuals. Cell Host & Microbe, inPress, ⟨10.1016/j.chom.2023.11.007⟩. ⟨hal-04325463⟩