Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria
Abstract Background Vaccination 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 expressio...
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doaj-e61e4b856b15477aac6dea0f2e1475662021-01-31T16:37:01ZengBMCMalaria Journal1475-28752020-01-0119111410.1186/s12936-020-3130-2Vaccination accelerates hepatic erythroblastosis induced by blood-stage malariaDenis Delic0Frank Wunderlich1Saleh Al-Quraishy2Abdel-Azeem S. Abdel-Baki3Mohamed A. Dkhil4Marcos J. Araúzo-Bravo5Department of Biology, Heinrich-Heine-UniversityDepartment of Biology, Heinrich-Heine-UniversityDepartment of Zoology, College of Science, King Saud UniversityDepartment of Zoology, College of Science, King Saud UniversityBoehringer Ingelheim PharmaGroup of Computational Biology and Systems Biomedicine, Biodonostia Health Research InstituteAbstract Background Vaccination 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. Methods Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106 P. 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. Results Global 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. Conclusion The 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.https://doi.org/10.1186/s12936-020-3130-2LiverBlood-stage malariaPlasmodium chabaudiProtective vaccinationExtramedullary erythropoiesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Denis Delic Frank Wunderlich Saleh Al-Quraishy Abdel-Azeem S. Abdel-Baki Mohamed A. Dkhil Marcos J. Araúzo-Bravo |
spellingShingle |
Denis Delic Frank Wunderlich Saleh Al-Quraishy Abdel-Azeem S. Abdel-Baki Mohamed A. Dkhil Marcos J. Araúzo-Bravo Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria Malaria Journal Liver Blood-stage malaria Plasmodium chabaudi Protective vaccination Extramedullary erythropoiesis |
author_facet |
Denis Delic Frank Wunderlich Saleh Al-Quraishy Abdel-Azeem S. Abdel-Baki Mohamed A. Dkhil Marcos J. Araúzo-Bravo |
author_sort |
Denis Delic |
title |
Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria |
title_short |
Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria |
title_full |
Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria |
title_fullStr |
Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria |
title_full_unstemmed |
Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria |
title_sort |
vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2020-01-01 |
description |
Abstract Background Vaccination 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. Methods Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106 P. 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. Results Global 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. Conclusion The 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. |
topic |
Liver Blood-stage malaria Plasmodium chabaudi Protective vaccination Extramedullary erythropoiesis |
url |
https://doi.org/10.1186/s12936-020-3130-2 |
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