See the published version of this preprint at Malaria Journal.
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Denis Delic
Boehringer Ingelheim GmbH
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0233-8374
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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.
Keywords
Liver, blood-stage malaria, Plasmodium chabaudi, protective vaccination, extramedullary erythropoiesis
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View the published article at Malaria Journal.
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Posted 20 Jan, 2020
No community comments so far
Editorial decision: Accept
On 17 Jan, 2020
Editor assigned
On 16 Jan, 2020
Submission checks complete
On 15 Jan, 2020
Editor invited
On 15 Jan, 2020
No comments provided
Editorial decision: Minor Revision
On 14 Jan, 2020
Editor assigned
On 13 Jan, 2020
Submission checks complete
On 12 Jan, 2020
Editor invited
On 12 Jan, 2020
No comments provided
Editorial decision: Minor Revision
On 22 Dec, 2019
Review #2 received
Received 18 Dec, 2019
Review #1 received
Received 18 Dec, 2019
Reviewer #2 agreed
On 13 Dec, 2019
Reviewer #1 agreed
On 27 Nov, 2019
Reviewers invited
Invitations sent on 26 Nov, 2019
Editor assigned
On 21 Nov, 2019
First submitted
On 20 Nov, 2019
Submission checks complete
On 20 Nov, 2019
Editor invited
On 20 Nov, 2019
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Subject Areas
Infectious Diseases
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See the published version of this preprint at Malaria Journal.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Denis Delic
Boehringer Ingelheim GmbH
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0233-8374
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Malaria Journal.
Version 3
Posted 20 Jan, 2020
No community comments so far
Editorial decision: Accept
On 17 Jan, 2020
Editor assigned
On 16 Jan, 2020
Submission checks complete
On 15 Jan, 2020
Editor invited
On 15 Jan, 2020
No comments provided
Editorial decision: Minor Revision
On 14 Jan, 2020
Editor assigned
On 13 Jan, 2020
Submission checks complete
On 12 Jan, 2020
Editor invited
On 12 Jan, 2020
No comments provided
Editorial decision: Minor Revision
On 22 Dec, 2019
Review #2 received
Received 18 Dec, 2019
Review #1 received
Received 18 Dec, 2019
Reviewer #2 agreed
On 13 Dec, 2019
Reviewer #1 agreed
On 27 Nov, 2019
Reviewers invited
Invitations sent on 26 Nov, 2019
Editor assigned
On 21 Nov, 2019
First submitted
On 20 Nov, 2019
Submission checks complete
On 20 Nov, 2019
Editor invited
On 20 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Malaria Journal.
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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