Unraveling methylation changes of host macrophages in Mycobacterium tuberculosis infection - 09/05/16

Doi : 10.1016/j.tube.2016.03.003

Lin Zheng ^a, Eric T.Y. Leung ^a, H.K. Wong ^b, Grace Lui ^c, Nelson Lee ^c, Ka-Fai To ^d, K.W. Choy ^b, Raphael C.Y. Chan ^a, Margaret Ip ^a,^⁎
^a Department of Microbiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
^b Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
^c Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
^d Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region

^∗Corresponding author. Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, New Territories, Hong Kong Special Administrative Region. Tel.: +852 2632 1265; fax: +852 2647 3227.Department of MicrobiologyThe Chinese University of Hong KongPrince of Wales Hospital30-32 Ngan Shing St.ShatinNew TerritoriesHong Kong Special Administrative Region

Summary

Objectives

To characterize at high resolution DNA methylation changes of cytokines which occur in the genome of macrophages in association with Mycobacterium tuberculosis (MTB) infection

Methods

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.

Results

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.

Conclusions

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.

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Keywords : Mycobacterium tuberculosis, Beijing/W strains, Methylation, IL6R, IL17

Plan

Introduction

Materials and methods

Bacterial strains

Participant recruitment and patient characterization

IFN-γ release assay (IGRA) testing

PMBC isolation from whole blood

Infection of macrophages

DNA Methylation PCR arrays

MeDIP, agilent CpG island microarrays and data analysis

Bisulfite sequencing PCR (BSP) analysis

Data analysis

Results

Methylation profiles of different clinical MTB strains on THP-1 derived macrophages

Methylation profiles of human macrophages in different patient cohorts

Discussion

☆	Part of the data has been presented at the 114th General Meeting, American Society of Microbiology in Boston, 2014 (abstract no. D2085).

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Vol 98

P. 139-148 - mai 2016 Retour au numéro

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Unraveling methylation changes of host macrophages in Mycobacterium tuberculosis infection - 09/05/16

Summary

Objectives

Methods

Results

Conclusions

Plan

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