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High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Se requiere la señalización TLR para la virulencia de Salmonella typhimurium
Nicholas Arpaia1, Jernej Godec, Laura Lau
1Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Cell
|March 8, 2011
Resumen
Los receptores tipo peaje (TLR) son cruciales para el control de la infección por Salmonella typhimurium. Las señales inmunes innatas de los TLR regulan los genes de virulencia bacteriana esenciales para la supervivencia y la propagación sistémica.
Área de la Ciencia:
- Inmunología Inmunología.
- Microbiología Microbiología.
- Genética La genética.
Sus antecedentes:
- Los receptores Toll-like (TLR) juegan un papel clave en la defensa del huésped contra los patógenos microbianos.
- Los TLR pueden influir en la evolución de los mecanismos de virulencia de los patógenos.
- Salmonella typhimurium es un patógeno bacteriano intracelular que causa infecciones sistémicas.
Objetivo del estudio:
- Investigar la relación entre la resistencia del huésped y la virulencia del patógeno.
- Examinar el papel de los receptores de tipo Toll (TLR) en el control de la infección por Salmonella typhimurium.
- Para entender cómo las señales del sistema inmunológico innato regulan la expresión génica de virulencia bacteriana.
Principales métodos:
- Se usaron ratones con un gen nramp-1 funcional y que carecían de combinaciones de receptores similares a Toll (TLR).
- En ratones infectados con Salmonella typhimurium.
- Carga bacteriana evaluada, expresión génica de virulencia (SPI-2) y acidificación del fagosoma en células deficientes de TLR.
Principales resultados:
- Los ratones con deficiencia de TLR2 y TLR4 fueron muy susceptibles a Salmonella typhimurium.
- Los ratones que carecían de TLR adicionales involucrados en el reconocimiento de patógenos mostraron una susceptibilidad reducida.
- Salmonella typhimurium no logró regular los genes SPI-2 y formar compartimentos replicativos en las células deficientes en TLR.
- La señalización TLR mejora la acidificación del fagosoma, que es necesaria para la inducción de SPI-2.
Conclusiones:
- Salmonella typhimurium requiere señales del sistema inmune innato, mediado por TLRs, para regular los genes de virulencia.
- La acidificación del fagosoma mediada por TLR es crítica para la supervivencia intracelular bacteriana, el crecimiento y la infección sistémica.
- La comprensión de esta interacción puede informar estrategias para combatir las infecciones bacterianas.
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