Extensive differential DNA methylation between tuberculosis skin test positive and skin test negative cattle.

Autor: Bhat SA; UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland., Parveen A; UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland., Gormley E; UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland., Meade KG; UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland. kieran.meade@ucd.ie.; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland. kieran.meade@ucd.ie.; UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, C15 PW93, Ireland. kieran.meade@ucd.ie.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2024 Aug 06; Vol. 25 (1), pp. 762. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1186/s12864-024-10574-x
Abstrakt: Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), represents a significant problem for the agriculture industry as well as posing a risk for human health. Current diagnostic tests for bTB target the cell-mediated immune (CMI) response to infection with M. bovis, primarily through screening of animals with the tuberculin skin test. Epigenetic modifications have been shown to alter the course of the immune response and differentially methylated regions (DMRs) might also influence the outcome of the skin test in cattle. Whole Genome Bisulphite Sequencing (WGBS) was used to profile DNA methylation levels from peripheral blood of a group of cattle identified as test positive for M. bovis (positive for the single intradermal comparative tuberculin test (SICTT) and/or the interferon-γ release assay compared to a test negative control group [n = 8/group, total of 16 WGBS libraries]. Although global methylation profiles were similar for both groups across the genome, 223 DMRs and 159 Differentially Promoter Methylated Genes (DPMGs) were identified between groups with an excess of hypermethylated sites in SICTT positive cattle (threshold > 15% differential methylation). Genes located within these DMRs included the Interleukin 1 receptor (IL1R1) and MHC related genes (BOLA and BOLA-DQB). KEGG pathway analysis identified enrichment of genes involved in Calcium and MAPK signalling, as well as metabolism pathways. Analysis of DMRs in a subset of SICTT negative cattle that were IFN-γ positive showed differential methylation of genes including Interleukin 10 Receptor, alpha (IL10RA), Interleukin 17 F (IL17F) and host defence peptides (DEFB and BDEF109). This study has identified a number of immune gene loci at which differential methylation is associated with SICTT test results and the degree of methylation could influence effective host immune responses.
(© 2024. The Author(s).)
Databáze: MEDLINE
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