Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with mycobacterium tuberculosis

Ranjeet Kumar, Priyanka Halder, Sanjaya K. Sahu, Manish Kumar, Mandavi Kumari, Kuladip Jana, Zhumur Ghosh, Pawan Sharma, Manikuntala Kundu, Joyoti Basu

Research output: Contribution to journalArticle

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Abstract

Mycobacterium tuberculosis (M.tb.) replicates in host macrophages to cause tuberculosis. We have investigated the role of miRNAs in M.tb.-infected murine RAW264.7 cells and bone marrow-derived macrophages (BMDMs), focusing on miR-155, the most highly upregulated miRNA. We observed that miR-155 upregulation is directly linked to the attenuation of expression of BTB and CNC homology 1 (Bach1) and SH2-containing inositol 5′-phosphatase (SHIP1). Bach1 is a transcriptional repressor of haem oxygenase-1 (HO-1), whereas SHIP1 inhibits the activation of the serine/threonine kinase AKT. We hypothesize that M.tb.-induced miR-155 induction leads to repression of Bach1, which augments the expression of HO-1, a documented activator of the M.tb. dormancyregulon. SHIP1 repression facilitates AKT activation, which is required for M.tb. survival. In addition, M.tb.-induced miR-155 inhibits expression of cyclooxygenase-2 (Cox-2) and interleukin-6 (Il-6), two modulators of the innate immune response. Importantly, we observed that the virulence-associated secreted protein ESAT-6 plays a key role in miR-155 induction and its subsequent effects on Bach1 and SHIP1 repression. Inhibition of miR-155 hindered survival of M.tb. in RAW264.7 and in murine BMDMs. Thus, our results offer new insights into the role of miRNAs in modulation of the host innate immune response by M.tb. for its own benefit.

Original languageEnglish (US)
Pages (from-to)1620-1631
Number of pages12
JournalCellular Microbiology
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2012

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Mycobacterium tuberculosis
Macrophages
Infection
MicroRNAs
Heme Oxygenase (Decyclizing)
Innate Immunity
Protein-Serine-Threonine Kinases
Cyclooxygenase 2
Virulence
Interleukin-6
Tuberculosis
Up-Regulation
Proteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

Cite this

Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with mycobacterium tuberculosis. / Kumar, Ranjeet; Halder, Priyanka; Sahu, Sanjaya K.; Kumar, Manish; Kumari, Mandavi; Jana, Kuladip; Ghosh, Zhumur; Sharma, Pawan; Kundu, Manikuntala; Basu, Joyoti.

In: Cellular Microbiology, Vol. 14, No. 10, 01.10.2012, p. 1620-1631.

Research output: Contribution to journalArticle

Kumar, R, Halder, P, Sahu, SK, Kumar, M, Kumari, M, Jana, K, Ghosh, Z, Sharma, P, Kundu, M & Basu, J 2012, 'Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with mycobacterium tuberculosis', Cellular Microbiology, vol. 14, no. 10, pp. 1620-1631. https://doi.org/10.1111/j.1462-5822.2012.01827.x
Kumar, Ranjeet ; Halder, Priyanka ; Sahu, Sanjaya K. ; Kumar, Manish ; Kumari, Mandavi ; Jana, Kuladip ; Ghosh, Zhumur ; Sharma, Pawan ; Kundu, Manikuntala ; Basu, Joyoti. / Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with mycobacterium tuberculosis. In: Cellular Microbiology. 2012 ; Vol. 14, No. 10. pp. 1620-1631.
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AU - Kumari, Mandavi

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