| Induction of Serine Protease Inhibitor 9 by Mycobacterium tuberculosis Inhibits Apoptosis and Promotes Survival of Infected Macrophages. | |
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MedLine Citation:
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PMID: 22090449 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Zahra Toossi; Mianda Wu; Roxana Rojas; Barbara Kalsdorf; Htin Aung; Christina S Hirsch; Jessica Walrath; Angela Wolbink; Marieke van Ham; Richard F Silver |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-16 |
Journal Detail:
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Title: The Journal of infectious diseases Volume: - ISSN: 1537-6613 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Divisions of Infectious Diseases. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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