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Aberrant methylation of host macrophages induced by tuberculosis infection

  • Ava Behrouzi
  • Shima Hadifar
  • Amir Amanzadeh
  • Farhad Riazi Rad
  • Farzam Vaziri
  • Seyed Davar SiadatEmail author
Original Paper

Abstract

DNA methylation has been introduced as a promising biomarker for different diseases. Alterations in macrophage DNA methylation status have been documented during Mycobacterium tuberculosis (Mtb) infection. We conducted this study using a human methylation PCR array kit, which comprised a panel of 22 genes in TLR2 signaling pathway, in order to gain insights into epigenetic interactions between drug-susceptible and -resistant Mtb strains and THP-1-derived macrophages (one of the main host immunity cells during TB infection). We also evaluated the expression of Rv1988 gene in the studied isolates. It was found that the methylation level of all of the studied inflammatory genes, except Irak-2 and Tbk-1, increased in THP-1 macrophages, which were infected by extensively drug-resistant (XDR) Mtb strains, compared with the mock cells (P < 0.05). In susceptible strains, we only found hypomethylation in Irak-2 gene, in addition to a slight increase in the methylation levels of Ubev, Ube2n, and Traf6 genes. The present findings provide new insights into the potential role of resistant and susceptible Mtb strains in promoting aberrant epigenetic modifications in macrophages. Further investigations on the host epigenomes, infected with different Mtb isolates, are needed to elucidate their functions in immunological responses and to introduce new effective tools against Mtb infection.

Keywords

DNA methylation Mycobacterium tuberculosis THP1 Signaling pathway 

Abbreviations

Mtb

Mycobacterium tuberculosis

TLR

Toll-like receptor

MYD88

Myeloid differentiation primary response 88

IRAK

Interleukin receptor-associated

TRAF

Tumor necrosis factor receptor-associated factor 6

TOLLIP

Toll interacting protein

FADD

Foreign animal disease diagnostician

IRF

Interferon regulatory factor

MAP3K7

Mitogen-activated protein kinase 7

MIRU-VNTR

Mycobacterial interspersed repetitive units–variable number tandem repeat

RT-PCR

Reverse transcription-polymerase chain reaction

Notes

Acknowledgements

We would like to thank all the personnel of Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, for their assistance in this project.

Author contributions

AB practical work, data analysis, prepare and collection of main data. SH wrote the main manuscript text. AA contributed to practical work. FR contributed to data analysis. FV edit of final manuscript. SD design of project and edit of final manuscript. All authors read and approved the final manuscript.

Funding

This study was financially supported by Pasteur Institute of Iran (Grant No. 1006).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Ava Behrouzi
    • 1
    • 2
  • Shima Hadifar
    • 1
    • 2
  • Amir Amanzadeh
    • 3
  • Farhad Riazi Rad
    • 4
  • Farzam Vaziri
    • 1
    • 2
  • Seyed Davar Siadat
    • 1
    • 2
    Email author
  1. 1.Department of Mycobacteriology and Pulmonary ResearchPasteur Institute of IranTehranIran
  2. 2.Microbiology Research Center (MRC)Pasteur Institute of IranTehranIran
  3. 3.National Cell Bank of IranPasteur Institute of IranTehranIran
  4. 4.Department of ImmunologyPasteur Institute of IranTehranIran

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