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El BCG educa a las células madre hematopoyéticas para generar inmunidad innata protectora contra la tuberculosis
Eva Kaufmann1, Joaquin Sanz2, Jonathan L Dunn1
1Meakins-Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, Department of Pathology, McGill International TB Centre, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Cell
|January 13, 2018
Resumen
La memoria inmune innata, que antes se creía imposible, es generada por el entrenamiento de las células madre hematopoyéticas (HSC) de Bacillus Calmette-Guérin (BCG). Esta reprogramación mejora la protección de los macrófagos contra la tuberculosis.
Área de la Ciencia:
- Inmunología
- La hematopoyesis
- Enfermedades infecciosas
Sus antecedentes:
- La inmunidad adaptativa se consideraba tradicionalmente el único poseedor de la memoria inmune.
- La evidencia emergente sugiere que las células inmunes innatas pueden ser "entrenadas" para exhibir propiedades similares a la memoria.
- Los mecanismos y los sitios in vivo para la generación de memoria inmune innata siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Investigar los mecanismos y la ubicación de la formación de la memoria inmune innata in vivo.
- Para determinar si el Bacillus Calmette-Guérin (BCG) puede inducir una memoria inmune innata de larga duración.
- Explorar el potencial de las células madre hematopoyéticas (HSC) para el desarrollo de vacunas.
Principales métodos:
- Se administró BCG a ratones y se analizaron células madre hematopoyéticas (HSC) de médula ósea y células progenitoras multipotentes (MPP).
- Se utilizó el perfil de transcripción para evaluar los cambios en las HSC y las células progenitoras.
- Empleó modelos parabióticos y quiméricos de ratón, junto con la transferencia adoptiva, para rastrear el linaje y la función celular.
Principales resultados:
- El acceso de BCG a la médula ósea alteró los paisajes transcripcionales de HSC y MPP, promoviendo la mielopoyesis sobre la linfopoyesis.
- Los HSC formados por BCG producen macrófagos modificados epigenéticamente que confieren una mayor protección contra la virulenta Mycobacterium tuberculosis.
- La reprogramación de HSC inducida por BCG entrenó de manera sostenible el linaje de monocitos / macrófagos in vivo.
Conclusiones:
- La reprogramación de las células madre hematopoyéticas (HSC) por BCG establece la memoria inmune innata.
- Esta memoria inmune innata mediada por HSC mejora la protección contra la tuberculosis.
- Dirigirse al compartimento HSC representa una nueva estrategia para el desarrollo de vacunas.
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