Abstract
BackgroundVaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver.MethodsFemale Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106P. chabaudi-parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i.ResultsGlobal transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd, Rhag, Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1, Ahsp, Acyp1, Gata1, Gfi1b, Tal1, Klf1, Epor, and Cldn13. In vaccination-protected mice, expression of these genes, except Epb4.1, is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i., before declining towards the end of crisis phase on day 11 p.i.ConclusionThe present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1–2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi.
Highlights
Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi
Global transcriptomics analyses reveal modifications by vaccination of malaria‐induced hepatic gene expression on days 4 and 11 p.i The effect of protective vaccination on the time course of erythroid gene expression in the liver induced by P. chabaudi blood-stage malaria was analysed using mouse whole genome 8x60K oligo microarrays
This study provides evidence that vaccination, using a non-infectious vaccine consisting of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes, accelerates expression of erythroid genes in the liver induced by blood-stage malaria of P. chabaudi
Summary
Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i. Malaria has caused about 219 million cases and about 435,000 deaths globally in 2017, with about 266,000 deaths in children aged under 5 years [1]. The P. chabaudi model is appropriate to study effects of vaccination on the outcome of blood-stage malaria. Using an experimental non-infectious vaccine, survival of mice can be raised from 0% to over 80% [7, 8] This vaccine induces a healing course of otherwise lethal infections. Primary infections with 106 P. chabaudi-parasitized erythrocytes take a similar course in terms of parasitaemia in vaccinated and non-vaccinated mice of the inbred mouse strain Balb/c [8]. All non-vaccinated mice succumb to infection during crisis, whereas over 80% of the vaccinated mice survive the infections [8]
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