Induction of Serine Protease Inhibitor 9 by Mycobacterium tuberculosis Inhibits Apoptosis and Promotes Survival of Infected Macrophages

Our recent microarray analysis of infected human alveolar macrophages (AMs) found serine protease inhibitor 9 (PI-9) to be the most prominently expressed of a cluster of apoptosis-associated genes induced by virulent Mycobacterium tuberculosis. In the current study, we show that induction of PI-9 oc...

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Bibliographic Details
Published in:The Journal of infectious diseases 2012-01, Vol.205 (1), p.144-151
Main Authors: Toossi, Zahra, Wu, Mianda, Rojas, Roxana, Kalsdorf, Barbara, Aung, Htin, Hirsch, Christina S., Walrath, Jessica, Wolbink, Angela, van Ham, Marieke, Silver, Richard F.
Format: Article
Language:English
Subjects:
Alveolar macrophages
Apoptosis
BACTERIA
Bacteriology
Biological and medical sciences
Caspase 3 - metabolism
Cells, Cultured
Fundamental and applied biological sciences. Psychology
Humans
Infections
Infectious diseases
Macrophages, Alveolar - metabolism
Macrophages, Alveolar - microbiology
Major and Brief Reports
Medical sciences
Messenger RNA
Microbiology
Miscellaneous
Monocytes - metabolism
Monocytes - microbiology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - pathogenicity
Phagocytes
Proto-Oncogene Proteins c-bcl-2 - metabolism
RNA, Small Interfering - metabolism
Serpins - metabolism
Small interfering RNA
T lymphocytes
Transfection
Tuberculosis
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Summary:Our recent microarray analysis of infected human alveolar macrophages (AMs) found serine protease inhibitor 9 (PI-9) to be the most prominently expressed of a cluster of apoptosis-associated genes induced by virulent Mycobacterium tuberculosis. In the current study, we show that induction of PI-9 occurs within hours of infection with M. tuberculosis H37Rv and is maintained through 7 days of infection in both AMs and blood monocytes. Inhibition of PI-9 by small inhibitory RNA decreased M. tuberculosis-induced expression of the antiapoptotic molecule Bcl-2 and resulted in a corresponding increase in production of caspase 3, a terminal effector molecule of apoptosis. Further, PI-9 small inhibitory RNA mediated a significant reduction in the subsequent survival of M. tuberculosis within AMs. Thus PI-9 induction within human mononuclear phagocytes by virulent M. tuberculosis serves to protect these primary targets of infection from elimination by apoptosis and thereby promotes intracellular survival of the organism.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jir697