Unraveling methylation changes of host macrophages in Mycobacterium tuberculosis infection

Zheng, Lin; Leung, Eric; Wong, Heung‐wah; Lui, Grace; Lee, Nelson; To, Ka‐Fai; Choy, Kwong Wai; Chan, Raymond K. H.; Ip, Margaret

doi:10.1016/j.tube.2016.03.003

Cited by 57 publications

(39 citation statements)

References 51 publications

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“…Mounting evidence shows that epigenetics modulates host innate immunity against exogenous pathogens through multi-channel mechanisms involving in DNA methylation, histone post-translational modification and the activity of non-coding RNAs [28, 29]. For example, in mycobacterium tuberculosis infection, hyper-methylation located in promoter regions of IL17 family members has been observed in THP-1 monocytes [30]. Additionally, Histone H3K4me3 and H3K27me3 negatively regulate differentiation of monocytes in dendritic cells [31].…”

Section: Introductionmentioning

confidence: 99%

LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells

Chen

Lai

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The histone acetyltransferase HBO1 (Histone acetyltransferase binding to origin recognition complex 1, Myst2/Kat7) participates in a range of life processes including DNA replication and tumorigenesis. Recent studies revealed that HBO1 is involved in gene transcriptional activation. However, the molecular behavior of HBO1 in inflammation is yet to be studied. Here we report that endotoxin lipopolysaccharide (LPS) elevates HBO1 protein level via up-regulating UPS25 (ubiquitin specific peptidase 25) and alters inflammatory gene transcription in THP-1 monocytes and in human primary macrophages. LPS protects HBO1 from ubiquitin proteasomal degradation without significantly altering its transcription. By immunoprecipitation, we identified that HBO1 associates with a deubiquitinating enzyme USP25 in THP-1 cells. LPS increases protein level of USP25 resulting in accumulation of HBO1 by suppression of HBO1 ubiquitination. Stabilized-HBO1 modulates inflammatory gene transcription in THP-1 cells. These findings indicate that USP25 promotes stability of HBO1 in bacterial infection thereby enhances HBO1-mediated inflammatory gene transcription.

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Section: Introductionmentioning

confidence: 99%

LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells

Chen

Lai

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…Host epigenomic plasticity to M. tuberculosis has been reported previously 14,15 . Sharma 80 and colleagues showed that non-CpG loci in the host genome were hypermethylated following 81 reduced representation bisulfite sequencing (RRBS) analysis of THP-1 macrophages (a human 82 monocytic cell line) infected with M tuberculosis 14 .…”

mentioning

confidence: 76%

The bovine alveolar macrophage DNA methylome is resilient to infection withMycobacterium bovis

O’Doherty

Rue-Albrecht

Magee

et al. 2017

Preprint

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“…Pro-inflammatory cytokines including IFN-γ are produced from activated macrophages as response to toll like receptor-2(TLR-2) signaling pathway. In active tuberculosis, serum levels of these mediators and IFN-γ levels have been proved high in patients (11).Interferon gamma is one of the most important pro-inflammatory cytokines in many infectious or noninfectious chronic inflammatory diseases, and whole blood IFNassays are popular in diagnosis of human tuberculosis (17,18,19). In the current study, the results revealed highly significant elevation in serum IFN-γ level (Table 1) in newly diagnostic TB patients, relapse TB patients and healthy controls (P<0.001and P<0.014, respectively).…”

Section: Discussion: Serum Ifn-γ Levelmentioning

confidence: 99%

“…Un-methylated islands are related with actively transcripted gene, whereas methylated islands can bind with methylbinding proteins that up hold chromatin compaction and avoid the binding of transcription factors to these dinucleotide. Variations in the epigenome, and gene polymorphism of different ethnic groups control host susceptibility to TB infection (11). This epigenetic alteration may explain the host-pathogen interaction of M. tuberculosis and act as a biomarkers that decide what situation will be latency or disease (12).…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

al.¹

2019

Baghdad Sci.J

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Tuberculosis (TB) still remains an important medical problem due to high levels of morbidity and mortality worldwide. A series of innate immune mechanisms that create a cytokine network control the pathogenesis of tuberculosis and this response has the capacity to modify the host genomic DNA structure through epigenetic mechanisms such as DNA methylation which could constantly alter the local gene expression pattern that can modulate the metabolism of the tissues and the immune-response. Interferon-gamma (IFN-γ) is an important pro-inflammatory cytokine regulator of the innate immune response to TB. This study aims to determine DNA methylation patterns of INF-γ gene promoter and measure serum IFN- γ level in newly diagnosed TB patients, relapse TB patients, and healthy control, in order to study the possibility of using these as a biomarker for the prognosis of TB stages in patients. The current case-control study included 66 patients with TB and 33 healthy control subjects. DNA was extracted from peripheral blood(PB) of included subjects and modified using sodium bisulfate specific kit. DNA methylation patterns of IFN-γ gene promoter was determine by using methylation specific polymerase chain reaction(MS-PCR).Serum IFN-γ level was determined using enzyme linked immune-sorbent assay(ELISA). Results showed that percentages of DNA methylation patterns in normal controls, newly diagnostic TB patients and relapse TB patients were (63.3%, 18.2% and 21.2% respectively). Also, higher significant differences (P≤0.0001) of un-methylated IFN-γ gene promoter patterns in newly diagnostic TB patients than relapse TB patients comparison with healthy controls. The percentage of un-methylated DNA patterns in healthy controls, newly diagnostic TB patients and relapse TB patients were (9.9%, 39.4% and 51.5%, respectively). The mean of serum IFN-γ levels (pg/ml) for normal controls, newly diagnostic TB patients and relapse TB patients were (59.3± 13.8,75.8±24.3 and 69.6±18.7,respectively).In conclusion, there is a relative association between methylation of IFN-γ gene promoter and predisposing to TB progression.

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Unraveling methylation changes of host macrophages in Mycobacterium tuberculosis infection

Cited by 57 publications

References 51 publications

LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells

LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells

The bovine alveolar macrophage DNA methylome is resilient to infection withMycobacterium bovis

DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

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