Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis.
Published
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
Language
- eng
Conference Location
- United States