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La inflamación linfocítica crónica especifica el tropismo orgánico de los priones
Mathias Heikenwalder1, Nicolas Zeller, Harald Seeger
1Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
Science (New York, N.Y.)
|January 22, 2005
Resumen
La inflamación crónica puede hacer que los priones se acumulen en nuevos órganos. Esto ocurre a través de vías dependientes de las linfotoxinas, aumentando potencialmente los riesgos de transmisión de la enfermedad priónica.
Área de la Ciencia:
- Neuroinmunología La neuroinmunología.
- Biología del Prión Biología del Prión
- Investigación de la investigación de la patogénesis.
Sus antecedentes:
- Los priones (proteínas mal plegadas) suelen dirigirse a los tejidos nerviosos y linfoides.
- Las citoquinas proinflamatorias y las células inmunes son cruciales para la replicación de priones en los tejidos linfoides.
Objetivo del estudio:
- Para investigar si las condiciones inflamatorias influyen en la patogénesis de priones en órganos no linfoides.
- Determinar el papel de la inflamación en la expansión de la distribución del tejido priónico.
Principales métodos:
- Priones administrados a ratones con enfermedades inflamatorias inducidas de riñón, páncreas o hígado.
- Se analizó la acumulación de priones, la expresión de linfotoxinas y la presencia de células FDC-M1+ en tejidos inflamados.
- Examinó la patogénesis de priones en ratones con deficiencia de linfotoxina alfa o su receptor.
Principales resultados:
- La inflamación linfocítica crónica ha permitido la acumulación de priones en órganos previamente libres de priones.
- Los focos inflamatorios mostraron una correlación entre la regulación ascendente de las linfotoxinas y la inducción de células FDC-M1+ ectópicas.
- Los ratones que carecían de linfotoxina-alfa o su receptor no acumularon PrPSc ni mostraron infectividad.
Conclusiones:
- Las condiciones inflamatorias crónicas pueden expandir la distribución tisular de priones.
- La señalización de las linfotoxinas es crítica para la acumulación de priones en órganos inflamados no linfoides.
- La inflamación puede modificar la transmisión de las enfermedades priónicas.
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