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Título : Stable extracellular RNA fragments of Mycobacterium tuberculosis induce early apoptosis in human monocytes via a caspase-8 dependent mechanism
Autor : Obregón Henao, Andrés
Duque Correa, María Adelaida
Rojas López, Mauricio
García Moreno, Luis Fernando
Ortiz Reyes, Blanca Lucía
Brennan, Patrick J.
Belisle, John T
metadata.dc.subject.*: Apoptosis
Caspasa 8
Cromatografía de Afinidad
Chromatography, Affinity
Concanavalina A
Concanavalin A
Espacio Extracelular
Extracellular Space
Cinética
Kinetics
Monocitos
Monocytes
Mycobacterium tuberculosis
ARN Bacteriano
RNA, Bacterial
Sefarosa
Sepharose
Tuberculosis
Factor de Necrosis Tumoral alfa
Tumor Necrosis Factor-alpha
https://id.nlm.nih.gov/mesh/D017209
https://id.nlm.nih.gov/mesh/D053181
https://id.nlm.nih.gov/mesh/D002846
https://id.nlm.nih.gov/mesh/D003208
https://id.nlm.nih.gov/mesh/D005110
https://id.nlm.nih.gov/mesh/D007700
https://id.nlm.nih.gov/mesh/D009000
https://id.nlm.nih.gov/mesh/D009169
https://id.nlm.nih.gov/mesh/D012329
https://id.nlm.nih.gov/mesh/D012685
https://id.nlm.nih.gov/mesh/D014376
https://id.nlm.nih.gov/mesh/D014409
Fecha de publicación : 2012
Editorial : Public Library of Science
Citación : Obregón-Henao, Andrés et al. “Stable extracellular RNA fragments of Mycobacterium tuberculosis induce early apoptosis in human monocytes via a caspase-8 dependent mechanism.” PloS one vol. 7,1 (2012): e29970. doi:10.1371/journal.pone.0029970
Resumen : ABSTRACT: The molecular basis of pathogen-induced host cell apoptosis is well characterized for a number of microorganisms. Mycobacterium tuberculosis is known to induce apoptosis and it was shown that live but not heat killed M. tuberculosis stimulates this biological pathway in monocytes. The dependence of this activity on live bacilli led us to hypothesize that products released or secreted by M. tuberculosis are the primary apoptotic factors for human monocytes. Thus, the culture filtrate of in vitro grown M. tuberculosis strain H37Rv was fractioned by conventional chromatography and the apoptosis-inducing activity of individual fractions was measured on human monocytes. The tests employed included measurement of cell membrane damage, caspase activation, and cytokine release. Small molecular weight RNAs of M. tuberculosis were recognized as the predominant apoptosis inducing factors. The RNA was comprised primarily of tRNA and rRNA fragments that stably accumulate in the culture filtrate during early log-phase growth. The RNA fragments signaled through a caspase-8 dependent, caspase-1 and TNF-α independent pathway that ultimately compromised the human monocytes' ability to control M. tuberculosis infection. These studies provide the first report of bacterial RNA inducing apoptosis. They also provide a foundation to pursue pathways for secretion or release of nucleic acids from M. tuberculosis and the impact of secreted RNA fragments on pathogenesis.
metadata.dc.identifier.eissn: 1932-6203
metadata.dc.identifier.doi: 10.1371/journal.pone.0029970
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