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La islas de patogenicidad de la salmonela dependen de la evasión 2-dependiente del fagocito NADPH oxidasa
A Vazquez-Torres1, Y Xu, J Jones-Carson
1Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Science (New York, N.Y.)
|March 4, 2000
Resumen
Salmonella typhimurium utiliza su sistema de secreción SPI2 para evadir la muerte de los macrófagos. El bloqueo de la enzima NADPH oxidasa restauró la supervivencia bacteriana, lo que indica que SPI2 interfiere con los mecanismos de defensa de las células inmunes.
Área de la Ciencia:
- Microbiología Microbiología.
- Inmunología Inmunología.
- La patogénesis bacteriana es la patogénesis bacteriana.
Sus antecedentes:
- El sistema de secreción de la isla de patogenicidad de Salmonella 2 (SPI2) tipo III es crucial para la virulencia de Salmonella y la supervivencia intracelular dentro de los macrófagos.
- Los macrófagos emplean mecanismos como el estallido respiratorio dependiente de la NADPH oxidasa para eliminar patógenos intracelulares.
Objetivo del estudio:
- Para investigar el papel de SPI2 en la evasión de Salmonella typhimurium de la matanza mediada por los macrófagos.
- Para determinar si SPI2 interfiere con el sistema de NADPH oxidasa durante la infección de los macrófagos.
Principales métodos:
- Utilizando cepas de Salmonella typhimurium con y sin SPI2 funcional2.
- Empleando modelos de infección de macrófagos para evaluar la supervivencia bacteriana.
- Manipulación de la actividad de la NADPH oxidasa en los macrófagos.
- Empleando microscopía ultrastructural e inmunofluorescencia para visualizar la localización de la NADPH oxidasa.
Principales resultados:
- SPI2 permite a Salmonella typhimurium resistirse a la muerte por el macrófago NADPH oxidasa.
- La abrogación del estallido respiratorio de la NADPH oxidasa restauró la supervivencia de las bacterias mutantes SPI2 dentro de los macrófagos y su virulencia en ratones.
- La microscopía reveló la NADPH oxidasa localizada cerca de vacuolas que contienen bacterias mutantes SPI2, pero no bacterias de tipo salvaje.
Conclusiones:
- El sistema de secreción SPI2 es un factor clave en la capacidad de Salmonella para contrarrestar las defensas inmunitarias innatas del huésped, específicamente la NADPH oxidasa.
- SPI2 probablemente funciona interrumpiendo el tráfico normal de vesículas que contienen NADPH oxidasa al fagosoma, evitando así la destrucción de patógenos.
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