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Las células eritroides CD71+ inmunosupresoras comprometen la defensa del huésped neonatal contra las infecciones
Shokrollah Elahi1, James M Ertelt, Jeremy M Kinder
1Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Nature
|November 8, 2013
Resumen
Los recién nacidos.
Área de la Ciencia:
- Inmunología Inmunología.
- El desarrollo neonatal.
- Mecanismos de defensa del huésped.
Sus antecedentes:
- Los recién nacidos exhiben una mayor susceptibilidad a las infecciones.
- La inmadurez de las células inmunes es una explicación primaria para la inmunidad neonatal comprometida.
- La variabilidad en las respuestas inmunes requiere una explicación unificada para la hiporrespuesta neonatal.
Objetivo del estudio:
- Para investigar las propiedades inmunosupresoras de las células eritroides CD71 (((+) en neonatos.
- Para aclarar el papel de la arginasa-2 en la inmunosupresión neonatal.
- Comprender la doble función de las células CD71 (((+) en la susceptibilidad a las infecciones y la protección.
Principales métodos:
- Co-cultivo de células inmunes adultas y neonatales.
- Transferencia de células adultas a ratones neonatales.
- Inhibición molecular de la arginasa-2 y suplementación con L-arginina.
- Ablación de las células CD71 (((+) en ratones neonatales.
- Estudios en ratones libres de gérmenes y tratados con antimicrobianos.
Principales resultados:
- Las células eritroides CD71 ((+) fisiológicamente enriquecidas en neonatos poseen distintas propiedades inmunosupresoras.
- Las células CD71 ((+) neonatales expresan arginasa-2, crucial para la inmunosupresión; su inhibición o la suplementación con L-arginina invierte este efecto.
- La ablación o reducción de las células CD71 (((+) en neonatos se correlaciona con una disminución de la inmunosupresión y un aumento de la resistencia a patógenos como Listeria monocytogenes y Escherichia coli.
- Las células CD71 ((+) protegen contra la inflamación intestinal excesiva causada por la colonización microbiana comensal después de la partición.
Conclusiones:
- La susceptibilidad neonatal a las infecciones no puede deberse únicamente a defectos intrínsecos de las células inmunes.
- CD71(+) las células eritroides juegan un papel crítico en el equilibrio de las respuestas inmunes en los recién nacidos, mitigando la inflamación de la colonización microbiana.
- Estos hallazgos sugieren una necesidad de desarrollo para la inmunosupresión en los recién nacidos, lo que afecta las estrategias para mejorar la defensa del huésped.
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