Mycobacterium tuberculosis increases IP-10 and MIG protein despite inhibition of IP-10 and MIG transcription

Tuberculosis (Edinb). 2011 Jan;91(1):26-35. doi: 10.1016/ Epub 2010 Dec 16.


Mycobacterium tuberculosis (MTB) has evolved methods to evade interferon-gamma (IFNγ) mediated protection. We sought to determine the effect of MTB infection on expression of IFNγ-inducible Protein 10 (IP-10) and Monokine Induced by IFNγ (MIG), two chemokines involved in host defense. MTB infection of THP-1 cells inhibited the transcription of IP-10 and MIG. A key mechanism for the inhibition is the disruption of binding of Signal Transduction and Activation of Transcription 1-alpha (STAT1α) to its cis-regulatory element, present in the 5'-flanking region of both IP-10 and MIG promoters. Use of inhibitors specific to the nuclear factor-kappa B (NFκB) and p38 mitogen-activated protein kinase (p38(mapk)) implicate these two signaling pathways in mediating the effect of MTB on the inhibition of IFNγ-induced IP-10 and MIG mRNA expression. Interestingly, despite transcriptional inhibition, there was an unexpected increase in IP-10 and MIG protein production after combined IFNγ and MTB stimulation. MTB also inhibited IFNγ induction of MIG mRNA but augmented MIG protein in primary human monocyte-derived macrophages. The synergy between MTB and IFNγ in the induction of IP-10 and MIG protein appears to involve novel post-transcriptional events that incorporates non-canonical functions of NFκB and p38(mapk).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blotting, Northern
  • Cells, Cultured
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism*
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / immunology
  • Chemokine CXCL9 / metabolism*
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Mycobacterium tuberculosis / genetics*
  • NF-kappa B / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transcriptional Activation / genetics
  • Tuberculosis / genetics*
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • CXCL10 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • NF-kappa B
  • Interferon-gamma
  • p38 Mitogen-Activated Protein Kinases