Mycobacterium bovis Bacillus Calmette-Guérin (BCG) stimulates human β-defensin-2 gene transcription in human epithelial cells

Antimicrobial peptides produced by epithelial cells represent essential elements of innate immunity. Human β-defensin-2 (hβD-2) is a major inducible antimicrobial peptide which plays an important role in host defense. The goal of this study was to determine the effect of Mycobacterium bovis bacillus Calmette-Guérin (BCG) on hβD-2 gene expression in epithelial cells, and to characterize further the signaling pathways involved in hβD-2 induction in response to M. bovis BCG. Using reverse transcription-polymerase chain reaction (RT-PCR), hβD-2 mRNA expression was detected in pulmonary epithelial cells infected with M. bovis BCG. Furthermore, we found that M. bovis BCG-induced hβD-2 mRNA expression was sustained by endogenous TNF-α in A549 cells. Of note, hβD-2 induction by M. bovis BCG was not blocked by pretreatment with anti-IL6 antibody. Moreover, hβD-2 mRNA expression was regulated at a transcriptional level, since hβD-2 induction by M. bovis BCG was blocked by two inhibitors of NF-κB. Taken together, these results suggest that M. bovis BCG infection of human epithelial cells induces hβD-2 mRNA expression which is up-regulated by TNF-α produced from M. bovis BCG-infected cells, and is modulated by NF-κB. Studies of hβD-2 mRNA regulation in epithelial cells infected with M. bovis BCG provide insight into how its expression may be enhanced to control Mycobacterium tuberculosis infection.