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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
Author(s) -
Ganguly Niladri,
Giang Pham H,
Gupta Chitra,
Basu Sandip K,
Siddiqui Imran,
Salunke Dinakar M,
Sharma Pawan
Publication year - 2008
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/sj.icb.7100117
Subject(s) - transactivation , downregulation and upregulation , reactive oxygen species , secretory protein , biology , lipopolysaccharide , microbiology and biotechnology , chemistry , gene expression , gene , biochemistry , immunology
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.