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El receptor tipo peaje 3 promueve la iniciación cruzada a las células infectadas por el virus
Oliver Schulz1, Sandra S Diebold, Margaret Chen
1Immunobiology Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Nature
|February 16, 2005
Resumen
El ARN de doble cadena (dsRNA) en las células infectadas por el virus activa las células dendríticas a través del receptor tipo peaje 3 (TLR3), promoviendo el cruce de las células T citotóxicas (CTL). Esta vía dependiente de TLR3 mejora las respuestas CTL contra los antígenos asociados a las células durante las infecciones virales.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Virología Virología.
Sus antecedentes:
- La presentación cruzada de antígenos asociados a las células es crucial para las respuestas de las células T CD8 +.
- Las células dendríticas son las células presentadoras de antígenos (APC) clave en la presentación cruzada.
- Las señales que determinan la primarización cruzada de células T frente a la tolerancia cruzada siguen sin estar claras.
Objetivo del estudio:
- Para dilucidar el mecanismo que promueve la transmisión cruzada de células T citotóxicas (CTL) durante las infecciones virales.
- Para identificar las señales que dictan si la presentación del antígeno conduce a la activación o inactivación de CTL.
- Investigar el papel del ARN de doble cadena (dsRNA) y el receptor tipo peaje 3 (TLR3) en este proceso.
Principales métodos:
- Activación de las células dendríticas murinas CD8alpha+ por el dsRNA de las células infectadas.
- Evaluación de la activación de las células dendríticas a través de la fagocitosis y la señalización TLR3.
- Estudios de inmunización utilizando células infectadas por virus o dsRNA sintético para evaluar el cruce de CTL.
Principales resultados:
- El dsRNA en las células infectadas por virus, pero no en las células no infectadas, activa las células dendríticas.
- La activación de las células dendríticas requiere fagocitosis y señalización a través de TLR3.
- La inmunización con células infectadas o dsRNA aumenta significativamente el cruce primario de CTL.
- Este cross-priming es en gran medida dependiente de la expresión TLR3 por APCs.
Conclusiones:
- La activación de TLR3 por el dsRNA promueve la iniciación cruzada de CTL contra los antígenos asociados a las células.
- Este mecanismo es vital para montar respuestas CTL efectivas a los virus que no infectan directamente las células dendríticas.
- La señalización TLR3 proporciona un vínculo crítico entre la detección de infecciones virales y la inmunidad antiviral adaptativa.
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