PLASMODIUM CELL TROPISM: FROM INVASION TO PATHOLOGY

Abstract

Erythrocytes, the target cells of malarial parasites, are phenotypically diverse and range from immature reticulocytes to mature normocytes. The human-infecting Plasmodium falciparum and P. vivax prefer to invade reticulocytes, but the mechanisms behind reticulocyte tropism are unclear. Here, we developed an ex vivo assay which allows for unbiased tropism measurements of rodent malaria. We identified P. berghei ANKA and P. yoelii 17X1.1 to have the greatest reticulocyte preference and can be useful tools to study reticulocyte invasion. We then explored various forms of invasion inhibitions to identify potential reticulocyte receptors. Additionally, we encountered a unique erythrocyte phenotype in malaria-infected mice. This phenotype was systemic and globally affected host reticulocytes. Deeper investigations revealed that the phenotype arose due to accelerated CD71 loss and CD98 retention. Considering that most Plasmodium species prefer to invade reticulocytes, such systemic remodeling could have a profound impact on disease progression, and therefore warrants further exploration.