Gene expression of the liver of vaccination-protected mice in response to early patent infections of Plasmodium chabaudi 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 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.

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Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

10.21203/rs.2.17716/v2 ◽

2020 ◽

Author(s):

Denis Delic ◽

Frank Wunderlich ◽

Saleh Al-Quraishy ◽

Abdel-Azeem S. Abdel-Baki ◽

Mohamed A. Dkhil ◽

...

Keyword(s):

Gene Expression ◽

Blood Stage ◽

Host Cells ◽

Hepatic Expression ◽

Gene Expression Microarrays ◽

Expression Microarrays ◽

Final Survival ◽

Blood Stage Malaria ◽

Maximal Expression ◽

Lethal Blood

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 10 6 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 .

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Blood-stage malaria of Plasmodium chabaudi induces differential Tlr expression in the liver of susceptible and vaccination-protected Balb/c mice

Parasitology Research ◽

10.1007/s00436-016-4923-7 ◽

2016 ◽

Vol 115 (5) ◽

pp. 1835-1843 ◽

Cited By ~ 3

Author(s):

Saleh Al-Quraishy ◽

Mohamed A. Dkhil ◽

Suliman Alomar ◽

Abdel Azeem S. Abdel-Baki ◽

Denis Delic ◽

...

Keyword(s):

Blood Stage ◽

Plasmodium Chabaudi ◽

Blood Stage Malaria

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Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

10.21203/rs.2.17716/v3 ◽

2020 ◽

Author(s):

Denis Delic ◽

Frank Wunderlich ◽

Saleh Al-Quraishy ◽

Abdel-Azeem S. Abdel-Baki ◽

Mohamed A. Dkhil ◽

...

Keyword(s):

Gene Expression ◽

Blood Stage ◽

Host Cells ◽

Hepatic Expression ◽

Gene Expression Microarrays ◽

Expression Microarrays ◽

Final Survival ◽

Blood Stage Malaria ◽

Maximal Expression ◽

Lethal Blood

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.

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Suppression of Plasmodium chabaudi Parasitemia Is Independent of the Action of Reactive Oxygen Intermediates and/or Nitric Oxide

Infection and Immunity ◽

10.1128/iai.72.11.6359-6366.2004 ◽

2004 ◽

Vol 72 (11) ◽

pp. 6359-6366 ◽

Cited By ~ 18

Author(s):

Brad M. Gillman ◽

Joan Batchelder ◽

Patrick Flaherty ◽

William P. Weidanz

Keyword(s):

Nitric Oxide ◽

Xanthine Oxidase ◽

Time Course ◽

Blood Stage ◽

Plasmodium Chabaudi ◽

Oxygen Intermediates ◽

Xanthine Oxidase Inhibitor ◽

Nos Inhibitors ◽

Peak Parasitemia ◽

Blood Stage Malaria

ABSTRACT The killing of blood-stage malaria parasites in vivo has been attributed to reactive intermediates of oxygen (ROI) and of nitrogen (RNI). However, in the case of the latter, this contention is challenged by recent observations that parasitemia was not exacerbated in nitric oxide synthase (NOS) knockout (KO) (NOS2−/− or NOS3−/−) mice or in mice treated with NOS inhibitors. We now report that the time course shows that Plasmodium chabaudi parasitemia in NADPH oxidase KO (p47phox−/−) mice also was not exacerbated, suggesting a minimal role for ROI-mediated killing of blood-stage parasites. It is possible that the production of protective antibodies during malaria may mask the function of ROI and/or RNI. However, parasitemia in B-cell-deficient JH −/− × NOS2−/− or JH −/− × p47phox−/− mice was not exacerbated. In contrast, the magnitude of peak parasitemia was significantly enhanced in p47phox−/− mice treated with the xanthine oxidase inhibitor allopurinol, but the duration of patent parasitemia was not prolonged. Whereas the time course of parasitemia in NOS2−/− × p47phox−/− mice was nearly identical to that seen in normal control mice, allopurinol treatment of these double-KO mice also enhanced the magnitude of peak parasitemia. Thus, ROI generated via the xanthine oxidase pathway contribute to the control of ascending P. chabaudi parasitemia during acute malaria but alone are insufficient to suppress parasitemia to subpatent levels. Together, these results indicate that ROI or RNI can contribute to, but are not essential for, the suppression of parasitemia during blood-stage malaria.

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