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Un mecanismo inmune innato dependiente de FADD en las células de mamíferos

Siddharth Balachandran¹, Emmanuel Thomas, Glen N Barber

¹Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.

|November 19, 2004

Resumen

Las células de mamíferos que carecen de la proteína FADD muestran una expresión génica antiviral deteriorada y son susceptibles a las infecciones virales. Esto pone de relieve el FADD.

Área de la Ciencia:

Inmunología Inmunología.
Virología Virología.
Biología Molecular Biología Molecular

Sus antecedentes:

La inmunidad innata de los vertebrados es crucial para la defensa contra los patógenos.
El ARN de doble cadena (dsRNA) de la replicación viral desencadena respuestas inmunes innatas.
El papel de FADD en la inmunidad antiviral mediada por dsRNA no se entiende completamente.

Objetivo del estudio:

Para investigar el papel de FADD en la expresión génica intracelular activada por dsRNA.
Para dilucidar la vía de señalización involucrada en la defensa antiviral mediada por FADD.

Principales métodos:

Análisis de la expresión génica en células de mamíferos que carecen de FADD.
Investigación de los componentes de señalización que incluyen TLR3, PKR, RIPK1, TBK1 e IRF-3.
Comparación con las vías inmunológicas innatas en Drosophila.

Principales resultados:

Las células de mamíferos deficientes en FADD exhiben una expresión génica defectuosa activada por ARNds, incluida la producción de interferón de tipo I.
Estas células deficientes de FADD son muy susceptibles a las infecciones virales.
La vía FADD es independiente de TLR3 y PKR, pero requiere la activación IRF-3 mediada por RIPK1 y TBK1.

Conclusiones:

FADD es esencial para la inducción óptima de interferones de tipo I y otros genes antivirales en las células de mamíferos.
Existe una vía de reconocimiento de patógenos dependiente de FADD conservada en los mamíferos, similar a la Drosophila.
Esta vía es crítica para la defensa efectiva del huésped contra los patógenos virales.

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