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La intoxicación por AMP cíclica de los macrófagos por una Mycobacterium tuberculosis adenilato ciclase
Nisheeth Agarwal1, Gyanu Lamichhane, Radhika Gupta
1Department of Medicine, Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA.
Nature
|June 12, 2009
Resumen
Las bacterias de la tuberculosis entregan AMP cíclico (cAMP) a las células huésped utilizando una enzima específica (Rv0386). Este cAMP bacteriano interrumpe la señalización inmune, ayudando a la supervivencia y persistencia de la tuberculosis.
Área de la Ciencia:
- Microbiología Microbiología.
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La tuberculosis (TB) sigue siendo una gran amenaza para la salud mundial, causando millones de muertes al año.
- Mycobacterium tuberculosis (M.tb) infecta los macrófagos del huésped, alterando el entorno celular para su supervivencia.
- El mecanismo detrás del estallido de AMP cíclico (cAMP) observado en los macrófagos durante las infecciones micobacterianas no se entiende completamente.
Objetivo del estudio:
- Para investigar el papel de los genes de adenilato ciclasa en la virulencia de M.tb.
- Para dilucidar el mecanismo de la entrega de cAMP derivado de bacterias en los macrófagos del huésped.
- Comprender cómo el cAMP bacteriano influye en las respuestas inmunes del huésped y la supervivencia bacteriana.
Principales métodos:
- Cribado de 17 genes de adenilato ciclasa en M.tb para la virulencia.
- Evaluación del impacto de la deleción de Rv0386 en la entrega de cAMP a los macrófagos.
- Analizando los efectos de la reducción de la cAMP intramacrófago en la producción de TNF-alfa, la inmunopatología y la supervivencia bacteriana.
Principales resultados:
- Identificó Rv0386 como un gen crucial de adenilato ciclasa para la virulencia de M.tb.
- Se demostró que Rv0386 facilita la entrega de cAMP bacteriano en el citoplasma de los macrófagos.
- Se demostró que la pérdida de Rv0386 y la posterior reducción de la cAMP intramacrófago disminuyeron la producción de TNF-alfa, la inmunopatología y la supervivencia bacteriana.
Conclusiones:
- El cAMP derivado de bacterias, suministrado por Rv0386, juega un papel importante en la modulación de las respuestas inmunes del huésped.
- M.tb utiliza el cAMP bacteriano para manipular su entorno intracelular y tisular, promoviendo la supervivencia a largo plazo.
- Dirigirse a la administración de cAMP bacteriana podría ser una estrategia potencial para controlar la tuberculosis.
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