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- Title
Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis.
- Authors
Hinchey, Joseph; Lee, Sunhee; Jeon, Bo Y; Basaraba, Randall J; Venkataswamy, Manjunatha M; Chen, Bing; Chan, John; Braunstein, Miriam; Orme, Ian M; Derrick, Steven C; Morris, Sheldon L; Jacobs, William R, Jr; Porcelli, Steven A
- Abstract
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.
- Publication
The Journal of clinical investigation, 2007, Vol 117, Issue 8, p2279
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI31947