Abstract
Erythropoiesis and megakaryo-/thrombopoiesis occur in the bone marrow proceeding from common, even bipotent, progenitor cells. Recently, we have shown that protective vaccination accelerates extramedullary hepatic erythroblastosis in response to blood-stage malaria of Plasmodium chabaudi. Here, we investigated whether protective vaccination also accelerates extramedullary hepatic megakaryo-/thrombopoiesis. Female Balb/c mice were twice vaccinated with a non-infectious vaccine before infecting with 106 P. chabaudi-parasitized erythrocytes. Using gene expression microarrays and quantitative real-time PCR, transcripts of genes known to be expressed in the bone marrow by cells of the megakaryo-/thrombocytic lineage were compared in livers of vaccination-protected and unprotected mice on days 0, 1, 4, 8, and 11 p.i. Livers of vaccination-protected mice responded with expression of megakaryo-/thrombocytic genes faster to P. chabaudi than those of unvaccinated mice, evidenced at early patency on day 4 p.i., when livers exhibited significantly higher levels of malaria-induced transcripts of the genes Selp and Pdgfb (p-values < 0.0001), Gp5 (p-value < 0.001), and Fli1, Runx1, Myb, Mpl, Gp1ba, Gp1bb, Gp6, Gp9, Pf4, and Clec1b (p-values < 0.01). Together with additionally analyzed genes known to be related to megakaryopoiesis, our data suggest that protective vaccination accelerates liver-intrinsic megakaryo-/thrombopoiesis in response to blood-stage malaria that presumably contributes to vaccination-induced survival of otherwise lethal blood-stage malaria.
Highlights
Introduction iationsMalaria is still a threat to human health in tropical countries
The expression dynamics of megakaryocyte-related genes in response to blood-stage malaria were investigated in the liver of non-vaccinated and vaccination-protected mice
We found four main types of trajectories: a few genes followed constant or decreasing trajectories; Stat3 and Etv6 had a shot of expression on day 1 p.i.; a set from Selp to Clec1b presented strongly increasing trajectories; and another set from Gp6 to Gp1bb presented increasing trajectories but with strong differences on certain days between vaccinated and unvaccinated samples
Summary
Introduction iationsMalaria is still a threat to human health in tropical countries. In 2019, there were an estimated 229 million cases and 409,000 deaths globally [1]. Morbidity and mortality of malaria are caused by the blood-stages of parasitic protozoans of the genus Plasmodium, which invade and multiply in host red blood cells. Plasmodium species, causing about 99% of global malaria-related deaths [2]. An anti-malaria vaccine with an efficacy of more than 50%, neither against P. falciparum nor any other human malaria species, is yet to be commercially available [3,4]. P. falciparum shares several characteristics with P. chabaudi in mice, which is a convenient experimental system to study the host defense and its responses to vaccination against blood-stage malaria [5,6]. In this model, vaccination with a non-infectious vaccine, consisting of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes, induces
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