Abstract
Circulating red blood cells consist of young erythrocytes (early and late reticulocytes) and mature erythrocytes (normocytes). The human malaria parasites, Plasmodium falciparum and P. vivax, have a preference to invade reticulocytes during blood-stage infection. Rodent malaria parasites that also prefer reticulocytes could be useful tools to study human malaria reticulocyte invasion. However, previous tropism studies of rodent malaria are inconsistent from one another, making it difficult to compare cell preference of different parasite species and strains. In vivo measurements of cell tropism are also subjected to many confounding factors. Here we developed an ex vivo tropism assay for rodent malaria with highly purified fractions of murine reticulocytes and normocytes. We measured invasion into the different erythrocyte populations using flow cytometry and evaluated the tropism index of the parasite strains. We found that P. berghei ANKA displayed the strongest reticulocyte preference, followed by P. yoelii 17X1.1, whereas P. chabaudi AS and P. vinckei S67 showed mixed tropism. These preferences are intrinsic and were maintained at different reticulocyte and normocyte availabilities. Our study shed light on the true erythrocyte preference of the parasites and paves the way for future investigations on the receptor-ligand interactions mediating erythrocyte tropism.
Highlights
Despite being enucleated, circulating erythrocytes are phenotypically diverse and range from young erythrocytes to fully matured biconcave erythrocytes
For simplicity and to have a clear distinction between reticulocytes and normocytes, here we only focus on the CD71+ CD98+ reticulocytes and CD71- CD98normocytes to measure erythrocyte tropism
P. berghei ANKA (PbA) and P. vinckei vinckei S67 (PvvS67), we measured tropism before the mice started to succumb to the infection
Summary
Despite being enucleated, circulating erythrocytes are phenotypically diverse and range from young erythrocytes (which consist of early and late reticulocytes) to fully matured biconcave erythrocytes (normocytes). Reticulocytes egress out of hematopoietic organs (primarily the bone marrow) into the peripheral circulation, where they only consist around 1-3% of total human erythrocytes (Chin-Yee et al, 1991). P. vivax, the most widespread human malaria species, has a stringent erythrocyte tropism and can only invade the most immature human reticulocytes (Malleret et al, 2015). P. falciparum, the deadliest human malaria species, has a preference for reticulocytes, but can invade normocytes too (Pasvol et al, 1980; Naidu et al, 2019). No reticulocyte-specific receptor for P. falciparum invasion has been identified so far (Cowman et al, 2017)
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