Roles of the Duffy antigen and glycophorin A in malaria infectionand erythrocyte.

We constructed gene knockout mice lacking either the Duffy antigen (Dfy) or glycophorin A (GPA), major glycoproteins that are expressed on erythrocyte membranes, to examine the role of these proteins in malaria infection and erythrocyte. All of the rodent malarias examined proliferated in the erythrocytes of these knockout mice, indicating that neither the Duffy antigen nor GPA has an essential role as a receptor for malaria parasites. Duffy antigen knockout mice infected by Plasmodium yoelii 17XL exhibited autotherapy. At the early stage of the infection, the parasite proliferated exponentially, whereas at the late stage, parasitemia decreased to a level at which the mice were considered cured. The results of depletion experiments with anti-CD4 antibodies suggested that CD4-positive cells in the Duffy antigen knockout mice were responsible for the autotherapy effect. The Duffy antigen is a chemokine receptor. Compared to wild-type mice, chemokines which have affinities for the Duffy antigen injected intravenously more rapidly disappeared from the Duffy antigen knockout mice. Stimulation of the immune response by the increase of leukocytes might lead to the suppression of parasitemia in the Duffy antigen knockout mice. The absence of GPA decreased the amount of O-linked oligosaccharides on the erythrocyte membranes. The erythrocyte membranes of the GPA knockout mice decreased several O-linked glycoproteins and TER-119 protein. GPA has an essential role in the expression of O-linked antigens on erythrocyte membranes, but these proteins are not important for malaria parasite invasion of erythrocytes.