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La inmunidad intrínseca celular se extiende a las células espectadoras a través de la transferencia intercelular de
Andrea Ablasser1, Jonathan L Schmid-Burgk, Inga Hemmerling
1Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital, University of Bonn, 53127 Bonn, Germany.
Nature
|October 1, 2013
Resumen
Las células inmunes comparten señales antivirales a través de las uniones gap. El GMP-AMP cíclico (cGAMP) sintetizado por la enzima cGAS viaja entre las células, activando STING y promoviendo la inmunidad antiviral sin depender de los interferones de tipo I.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los organismos multicelulares dependen de la colaboración celular para la defensa inmune innata contra los patógenos.
- El intercambio de información entre las células inmunes está mediado principalmente por factores proteicos solubles como las citocinas y las quimiocinas.
- Los interferones tipo I (IFN) son cruciales para alertar a las células de la presencia de patógenos e iniciar respuestas antivirales.
Objetivo del estudio:
- Para investigar el mecanismo de la comunicación intercelular en la inmunidad antiviral.
- Para determinar si las vías de detección del ADN citosólico implican la transferencia de señales de célula a célula.
- Explorar nuevas estrategias de hospedaje para una rápida defensa antiviral.
Principales métodos:
- Utilizó modelos de células murinas y humanas para estudiar la señalización inmune.
- Investigó el papel de las vías cíclicas de GMP-AMP (cGAMP) sintasa (cGAS) y STING.
- Examinó la transferencia de cGAMP ((2'-5') a través de las uniones de hueco y su efecto en la inmunidad de los transeúntes.
Principales resultados:
- Se descubrió que el cGAMP cGAS-sintetizado ((2'-5') se transfiere entre células adyacentes a través de uniones gap.
- Se demostró que la transferencia intercelular de cGAMP activa el STING en las células receptoras, confiriendo inmunidad antiviral.
- Se demostró que esta inmunidad de espectador opera independientemente de la señalización IFN de tipo I e involucra a varias conexiones.
Conclusiones:
- Se identificó un nuevo mecanismo de inmunidad antiviral horizontal, independiente de la transcripción.
- cGAMP{2'-5') a través de las uniones de brecha representa una estrategia de colaboración inmune rápida y localizada.
- Esta vía pone de relieve un aspecto no reconocido previamente de la coordinación de la defensa inmune innata.
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