Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice
Araúzo-Bravo, Saleh Al-Quraishy, Mohamed A. Dkhil, Abdel-Azeem S. Abdel-Baki, Foued Ghanjati, Lars Erichsen, Simeon Santourlidis, Frank Wunderlich, Marcos J. . 2017
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 DNAmethylation (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.
Background: Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in…
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