Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10: ESAT6 complex inhibit lipopolysaccharide-induced NF-κB transactivation by downregulation of reactive oxidative species (ROS) production

Niladri Ganguly, Pham H. Giang, Chitra Gupta, Sandip K. Basu, Imran Siddiqui, Dinakar M. Salunke, Pawan Sharma

Research output: Contribution to journalArticlepeer-review

Abstract

Mycobacterium tuberculosis (Mtb) causes death of 2-3 million people annually and is considered one of the most successful intracellular pathogens to persist inside the host macrophage. Recent studies have implicated the role of RD-1 region of Mtb genome in the mycobacterial pathogenesis. The role of RD-1-encoded secretory proteins of Mtb in modulation of macrophage function has not been investigated in detail. Here we show that RD-1 encoded two major secretory proteins, namely, culture filtrate protein-10 kDa (CFP-10) and early secreted antigenic target-6 kDa (ESAT-6), and their 1:1 CFP-10:ESAT6 complex inhibit production of reactive oxidative species (ROS) in RAW264.7 cells. These proteins also downregulated the bacterial lipopolysaccharide (LPS)-induced ROS production, which, in turn, downregulated LPS-induced nuclear factor-κB (NF-κB) p65 DNA-binding activity, as well as inhibited the NF-κB-dependent reporter gene (chloramphenicol acetyl transferase) expression in the treated macrophages. Moreover, addition of N-acetyl cysteine, which is a scavenger of ROS, also inhibited LPS-induced reporter gene expression by scavenging the ROS, thereby preventing NF-κB transactivation. These studies indicate that the secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex of Mtb can inhibit LPS-induced NF-κB-dependent gene expression via downregulation of ROS production.

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalImmunology and Cell Biology
Volume86
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • CFP-10
  • ESAT-6
  • Lipopolysaccharide
  • NF-κB
  • ROS

ASJC Scopus subject areas

  • Immunology
  • Clinical Biochemistry
  • Cell Biology

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