Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis.


Journal Article

The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. Deletion of secA2 markedly increased priming of antigen-specific CD8(+) T cells in vivo, and vaccination of mice and guinea pigs with a secA2 mutant significantly increased resistance to M. tuberculosis challenge compared with standard M. bovis bacille Calmette-Guérin vaccination. Our results define a mechanism for a key immune evasion strategy of M. tuberculosis and provide what we believe to be a novel approach for improving mycobacterial vaccines.

Full Text

Duke Authors

Cited Authors

  • Hinchey, J; Lee, S; Jeon, BY; Basaraba, RJ; Venkataswamy, MM; Chen, B; Chan, J; Braunstein, M; Orme, IM; Derrick, SC; Morris, SL; Jacobs, WR; Porcelli, SA

Published Date

  • August 2007

Published In

Volume / Issue

  • 117 / 8

Start / End Page

  • 2279 - 2288

PubMed ID

  • 17671656

Pubmed Central ID

  • 17671656

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI31947


  • eng

Conference Location

  • United States