title: Unraveling methylation changes of host macrophages in Mycobacterium tuberculosis infection.
abstract: To characterize at high resolution DNA methylation changes of cytokines which occur in the genome of macrophages in association with Mycobacterium tuberculosis (MTB) infection
  
  
  
  We studied the methylation profiles of THP-1 derived macrophage cells infected with clinical MTB strains [Beijing/W & non-Beijing/W lineage, sensitive (INH(S), RIF(S)) & resistant (INH(R), RIF(R)) strains] and of host macrophages from MTB infected cohorts (active & latent patients) with the human methylation CpG islands microarrays.
  
  
  
  Methylated modification on the promoter sequences of cytokines and their receptors were found to be associated with MTB infection in a strain- and host-dependent manner. Our epigenetic analyses revealed that infection with Beijing/W MTB strains enhanced IL6R, IL4R and IL17R hyper-methylations in infected macrophages. Validation of IL6R methylated sequence confirmed that MTB infection induced DNA methylation of CpG67 region in the IL6R promoter. In addition, studies on the human macrophage methylation profiles from the patient cohorts indicated that the methylation rate of IL17 family members and related genes were significantly altered in patients with active MTB infections.
  
  
  
  Our study offered novel insights into the epigenetic changes in the interaction of host macrophages in MTB infections and warrant further explorations into these changes in modulating the immune response in active and latent MTB infections.
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Eric T Y
authors.initials: ET
authors.lastname: Leung
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: H K
authors.initials: HK
authors.lastname: Wong
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Grace
authors.initials: G
authors.lastname: Lui
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Nelson
authors.initials: N
authors.lastname: Lee
authors.affiliation: Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: K W
authors.initials: KW
authors.lastname: Choy
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Raphael C Y
authors.initials: RC
authors.lastname: Chan
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: margaretip@cuhk.edu.hk.
authors.forename: Margaret
authors.initials: M
authors.lastname: Ip
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D018899:CpG Islands; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D054884:Host-Pathogen Interactions; D006801:Humans; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D055985:Latent Tuberculosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D011401:Promoter Regions, Genetic; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*
chemical_list: D016207:Cytokines; C109985:IL17RA protein, human; C504000:IL4R protein, human; C508603:IL6R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D019947:Receptors, Interleukin-6
keywords: Beijing/W strains; IL17; IL6R; Methylation; Mycobacterium tuberculosis