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

Joseph Hinchey, Sunhee Lee, Bo Y. Jeon, Randall J. Basaraba, Manjunatha M. Venkataswamy, Bing Chen, John Chan, Miriam Braunstein, Ian M. Orme, Steven C. Derrick, Sheldon L. Morris, William R. Jacobs, Steven A. Porcelli

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214 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2279-2288
Number of pages10
JournalJournal of Clinical Investigation
Volume117
Issue number8
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hinchey, J., Lee, S., Jeon, B. Y., Basaraba, R. J., Venkataswamy, M. M., Chen, B., Chan, J., Braunstein, M., Orme, I. M., Derrick, S. C., Morris, S. L., Jacobs, W. R., & Porcelli, S. A. (2007). Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. Journal of Clinical Investigation, 117(8), 2279-2288. https://doi.org/10.1172/JCI31947