Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice.
Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P. chabaudi malaria and, concomitantly, modifications of constitutive DNA methylation of promoters of numerous genes in the liver; specifically, promoters of 256 genes are hyper(=up)- and 345 genes are hypo(=down)-methylated (p < 0.05). Protective vaccination also leads to changes in promoter DNA methylation upon challenge with P. chabaudi at peak parasitemia on day 8 post infection (p.i.), when 571 and 1013 gene promoters are up- and down-methylated, respectively, in relation to constitutive DNA methylation (p < 0.05). Gene set enrichment analyses reveal that both vaccination and P. chabaudi infections mainly modify promoters of those genes which are most statistically enriched with functions relating to regulation of transcription. Genes with down-methylated promoters encompass those encoding CX3CL1, GP130, and GATA2, known to be involved in monocyte recruitment, IL-6 trans-signaling, and onset of erythropoiesis, respectively. Our data suggest that vaccination may epigenetically improve parts of several effector functions of the liver against blood-stage malaria, as, e.g., recruitment of monocyte/macrophage to the liver accelerated liver regeneration and extramedullary hepatic erythropoiesis, thus leading to self-healing of otherwise lethal P. chabaudi blood-stage malaria.
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. guraishi@yahoo.com.
Saleh
S
Al-Quraishy
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.|Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.
Mohamed A
MA
Dkhil
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.|Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Abdel-Azeem S
AS
Abdel-Baki
Epigenetics Core Laboratory, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Duesseldorf, Germany.
Foued
F
Ghanjati
Epigenetics Core Laboratory, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Duesseldorf, Germany.
Lars
L
Erichsen
Epigenetics Core Laboratory, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Duesseldorf, Germany.
Simeon
S
Santourlidis
Department of Biology, Heinrich-Heine-University, Duesseldorf, Germany.
Frank
F
Wunderlich
Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain.|IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
Marcos J
MJ
Araúzo-Bravo
D000818:Animals; D054428:Chemokine CX3CL1 / Q000096:biosynthesis / Q000235:genetics; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D050989:GATA2 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D018512:Parasitemia / Q000276:immunology; D016788:Plasmodium chabaudi / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014611:Vaccination
D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse; C494200:Il6st protein, mouse; D015850:Interleukin-6; D017780:Malaria Vaccines; D050822:Cytokine Receptor gp130
Blood-stage malaria; DNA methylation; Epigenetics; Liver; Plasmodium chabaudi; Protective vaccination