Global gene expression profiling, cytoadherence and immune evasion in Plasmodium yoelii blood-stage malaria parasites

摘要

Microarray studies using in vitro cultured blood-stage Plasmodium falciparum parasites reveal a 'just in time' gene expression cascade, implying that transcriptional patterns remain stable in the presence of external stressors. However, analysis of P. falciparum parasites isolated from infected patients suggests that parasite gene expression is modulated by host factors in vivo. We examined changes in gene expression of the rodent malaria parasite, Plasmodium yoelii 17X, while varying the in vivo environment. Using P. yoelii DNA microarrays, we examined differential gene expression in parasites from individual mice, from independent infections, at varying parasitemias and in the presence/absence of host antibody responses. We were interested in identifying coordinated changes in groups of genes associated with specific biological pathways. We also analyzed expression patterns of two multigene families in P. yoelii, the yir and pyst-a. Across experimental conditions, transcription was remarkably stable with little evidence for distinct transcriptional states or consistent changes in specific pathways. There was virtually no differential expression of the yir and pyst-a familes, although a relatively large number were expressed during blood-stage infection across experimental conditions.;P. falciparum parasites encode P. falciparum erythrocyte membrane protein-1 (PfEMPA) which is expressed on the infected red blood cell (RBC) surface and mediates adherence to receptors on host tissues. The RBC surface proteins that mediate adherence in other malaria species are unknown. Unlike P. falciparum, Plasmodium vivax infects immature human RBCs (i.e., reticulocytes). Reticulocytes are scarce in circulation, and reticulocyte-restricted parasites may adhere to sites of erythropoiesis for efficient host cell invasion. Using the reticulocyte-restricted parasite P. yoelii 17X, we developed an adherence assay that allows for isolation of parasites from adherent and non-adherent reticulocytes. Using DNA microarrays, we identified six genes whose expression was consistently associated with the adherence phenotype. We characterized three of these: PY06717, PY00074 and PY04120. We show that PY04120 localizes to the iRBC surface, and sera directed against PY04120 can block adherence of P. yoelii 17X infected reticulocytes to a murine brain endothelial cell line. These results indicate that PY04120 is a putative adhesin that contributes to iRBC adherence to host tissues.