Anaemia in Malaria: Premature removal of uninfected erythrocytes during blood-stage infection in mice

The aim of this project was to investigate the premature removal of uninfected erythrocytes during plasmodial infection, one of the three mechanisms contributing to the anaemia of malaria. A murine model of malaria infection was utilised for these studies. The leading theory proposed to explain the removal of uninfected red blood cells (RBCs) involves antibody (directed against parasite or self antigens) binding to erythrocytes and mediating their removal. Erythrophagocytosis of uninfected RBCs has been convincingly demonstated, however, although antibody can sometimes be detected on uninfected erythrocytes, it has not been shown to be pathogenic. The main technique used in the project followed the removal of an injected population of chromium labelled uninfected erythrocytes. The non-lethal Plasmodium yoelii (17x) parasite was utilised as this only infects reticulocytes. The rate of removal of the labelled RBCs (>98% mature) was, therefore, indicative of the elimination of uninfected erythrocytes from the circulation. This work employed SCID (deficient in T and B-cells) and nude (deficient in T-cells) mice to determine the effect of these immunodeficiencies. The results indicated that the removal of uninfected RBCs does occur in the absence of antibody, but not as rapidly as in normal mice. The passive transfer of serum from infected immunocompetent mice did not enhance the rate of removal in SCIDs. Measurements on macrophage activity showed no differences between SCID and normal mice to explain the delayed removal. Attempts to detect surface bound antibody on red blood cells (using Coombs and FACscan analysis) indicated that it is only detectable at low levels in a minority of samples. Antibody does not, therefore, appear to have a pathogenic role in the anaemia in this model. The emphasis should now be turned away from antibodies; alterations to the erythrocytes or changes in the physiology of the host, during infection, warrant greater investigation