Modification of the Host Epigenome by Parasitic Protists

Gendlina, Inessa; Monerri, Natalie Silmon de; Kim, Kami

doi:10.1007/978-3-319-55021-3_9

Cited by 2 publications

(2 citation statements)

References 168 publications

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“…In this sense, epigenomic modifications are particularly ligated to pathological processes behind the chronic phases of infections, even when the first stages have been overcome [21,22]. Several of these modifications have been described in infectious diseases like viral [23], bacterial [24] and specifically, DNAm changes has been reported in parasitic diseases, such as Malaria, Leishmaniasis and Chagas disease [16,25].…”

Section: Box Plots Of Three Of the Most Interesting Genes Comparing Dnam Levels Between Chronic Chagas Cardiomyopathy Patients (Ccc) And mentioning

confidence: 99%

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

et al. 2021

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A recent genome-wide association study (GWAS) identified a locus in chromosome 11 associated with the chronic cardiac form of Chagas disease. Here we aimed to elucidate the potential functional mechanism underlying this genetic association by analyzing the correlation among single nucleotide polymorphisms (SNPs) and DNA methylation (DNAm) levels as cis methylation quantitative trait loci (cis-mQTL) within this region. A total of 2,611 SNPs were tested against 2,647 DNAm sites, in a subset of 37 chronic Chagas cardiomyopathy patients and 20 asymptomatic individuals from the GWAS. We identified 6,958 significant cis-mQTLs (False Discovery Rate [FDR]<0.05) at 1 Mb each side of the GWAS leading variant, where six of them potentially modulate the expression of the SAC3D1 gene, the reported gene in the previous GWAS. In addition, a total of 268 cis-mQTLs showed differential methylation between chronic Chagas cardiomyopathy patients and asymptomatic individuals. The most significant cis-mQTLs mapped in the gene bodies of POLA2 (FDR = 1.04x10-11), PLAAT3 (FDR = 7.22x10-03), and CCDC88B (FDR = 1.89x10-02) that have been associated with cardiovascular and hematological traits in previous studies. One of the most relevant interactions correlated with hypermethylation of CCDC88B. This gene is involved in the inflammatory response, and its methylation and expression levels have been previously reported in Chagas cardiomyopathy. Our findings support the functional relevance of the previously associated genomic region, highlighting the regulation of novel genes that could play a role in the chronic cardiac form of the disease.

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Section: Box Plots Of Three Of the Most Interesting Genes Comparing Dnam Levels Between Chronic Chagas Cardiomyopathy Patients (Ccc) And mentioning

confidence: 99%

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

et al. 2021

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“…Epigenetic mechanisms regulate the interplay of host-pathogen interactions. Although information on epigenetic manipulation of hosts by Leishmania is scarce, the pathogen employs a number of stratagems to manipulate the host epigenome, thereby hijacking its cellular soldiers (23, 51, 52). Genetic heterogeneity among different Leishmania species causes altered gene expression in response to environmental conditions in the host, resulting in varied epigenetic mechanisms.…”

Section: Leishmania-induced Host Epigenetic Alterationsmentioning

confidence: 99%

Leishmania-Host Interactions—An Epigenetic Paradigm

2019

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Leishmaniasis is one of the major neglected tropical diseases, for which no vaccines exist. Chemotherapy is hampered by limited efficacy coupled with development of resistance and other side effects. Leishmania parasites elude the host defensive mechanisms by modulating their surface proteins as well as dampening the host's immune responses. The parasites use the conventional RNA polymerases peculiarly under different environmental cues or pressures such as the host's milieu or the drugs. The mechanisms that restructure post-translational modifications are poorly understood but altered epigenetic histone modifications are believed to be instrumental in influencing the chromatin remodeling in the parasite. Interestingly, the parasite also modulates gene expression of the hosts, thereby hijacking or dampening the host immune response. Epigenetic factor such as DNA methylation of cytosine residues has been incriminated in silencing of macrophage-specific genes responsible for defense against these parasites. Although there is dearth of information regarding the epigenetic alterations-mediated pathogenesis in these parasites and the host, the unique epigenetic marks may represent targets for potential anti-leishmanial drug candidates. This review circumscribes the epigenetic changes during Leishmania infection, and the epigenetic modifications they enforce upon the host cells to ensure a safe haven. The non-coding micro RNAs as post-transcriptional regulators and correlates of wound healing and toll-like receptor signaling, as well as prognostic biomarkers of therapeutic failure and healing time are also explored. Finally, we highlight the recent advances on how the epigenetic perturbations may impact leishmaniasis vaccine development as biomarkers of safety and immunogenicity.

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Modification of the Host Epigenome by Parasitic Protists

Cited by 2 publications

References 168 publications

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

Leishmania-Host Interactions—An Epigenetic Paradigm

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