title: Plasmodium yoelii uses the murine Duffy antigen receptor for chemokines as a receptor for normocyte invasion and an alternative receptor for reticulocyte invasion.
abstract: Erythrocyte invasion by malaria parasites is a complex multistep process involving parasite and erythrocyte receptors. It is a critical stage in the parasite life cycle and, therefore, a logical step in which to intervene to prevent or ameliorate disease. Rodent models of malaria, commonly Plasmodium yoelii, are frequently used for studies of malaria pathogenesis. Little is known, however, about the invasion machinery of rodent malaria parasites. We have found previously that mice congenic for a region of chromosome 1, containing the Duffy antigen/receptor for chemokines (DARC), have different susceptibility to P yoelii infection. Because P vivax, a human parasite, and P knowlesi, a simian parasite, use DARC to enter human erythrocytes, we sought to identify the role of the murine DARC in P yoelii invasion. Using a novel in vivo invasion assay and DARC knock-out mice, we found that DARC knock-out normocytes (mature erythrocytes) had negligible levels of P yoelii invasion compared with wild-type normocytes, demonstrating that DARC is a receptor for invasion of murine erythrocytes. In contrast, DARC knock-out reticulocytes were invaded at a rate similar to that for wild-type reticulocytes. We conclude that there is a DARC- independent pathway for reticulocyte invasion. These findings represent the first identification of a murine malaria receptor on erythrocytes and the first determination that different pathways of invasion exist on normocytes and reticulocytes. Because we show conservation of host-receptor interactions between rodent and human malaria, we can now use this model to identify how immunity can interfere with the invasion process.
authors.affiliation: Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA. christine.olver@colostate.edu
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Swardson-Olver
authors.forename: Tracey C
authors.initials: TC
authors.lastname: Dawson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burnett
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Peiper
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: Anne C
authors.initials: AC
authors.lastname: Avery
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002918:Chymotrypsin / Q000494:pharmacology; D004195:Disease Models, Animal; D004375:Duffy Blood-Group System; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology*; D006790:Host-Parasite Interactions; D008288:Malaria / Q000209:etiology / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D010967:Plasmodium yoelii / Q000254:growth & development / Q000472:pathogenicity*; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012156:Reticulocytes / Q000737:chemistry / Q000469:parasitology*; D014357:Trypsin / Q000494:pharmacology
chemical_list: C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D002918:Chymotrypsin; D014357:Trypsin