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

Antimicrobial peptides produced by epithelial cells represent essential elements of innate immunity. Human beta-defensin-2 (hbetaD-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 hbetaD-2 gene expression in epithelial cells, and to characterize further the signaling pathways involved in hbetaD-2 induction in response to M. bovis BCG. Using reverse transcription-polymerase chain reaction (RT-PCR), hbetaD-2 mRNA expression was detected in pulmonary epithelial cells infected with M. bovis BCG. Furthermore, we found that M. bovis BCG-induced hbetaD-2 mRNA expression was sustained by endogenous TNF-alpha in A549 cells. Of note, hbetaD-2 induction by M. bovis BCG was not blocked by pretreatment with anti-IL6 antibody. Moreover, hbetaD-2 mRNA expression was regulated at a transcriptional level, since hbetaD-2 induction by M. bovis BCG was blocked by two inhibitors of NF-kappaB. Taken together, these results suggest that M. bovis BCG infection of human epithelial cells induces hbetaD-2 mRNA expression which is up-regulated by TNF-alpha produced from M. bovis BCG-infected cells, and is modulated by NF-kappaB. Studies of hbetaD-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.