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El NLRP6 Inflammasome reconoce el ácido lipoteicoico y regula la infección del patógeno Gram-positivo
Hideki Hara1, Sergey S Seregin2, Dahai Yang1
1Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cell
|November 6, 2018
Resumen
El ácido lipoteicoico (LTA) activa el inflamatorio NLRP6, iniciando una respuesta inmune innata. Esta vía, que involucra a la caspasa-11 y la interleucina-18 (IL-18), agrava las infecciones bacterianas Gram-positivas.
Área de la Ciencia:
- Inmunología
- Microbiología
- Biología celular
Sus antecedentes:
- Los activadores y las funciones del NLRP6 no se comprenden completamente.
- Las bacterias Gram-positivas producen ácido lipoteicoico (LTA), un componente con efectos inmunomoduladores conocidos.
Objetivo del estudio:
- Para identificar el activador del inflamatorio NLRP6.
- Para aclarar el papel de NLRP6 en la inmunidad innata contra las infecciones bacterianas Gram-positivas.
Principales métodos:
- Se investigó la unión a LTA y la activación de NLRP6 en los macrófagos.
- Se utilizaron modelos de ratón con knockout de Nlrp6 (Nlrp6-/-) y knockout de Caspase-11 (Casp11-/).
- Se evaluó la susceptibilidad a la infección por Listeria monocytogenes y se midió la producción de citoquinas.
Principales resultados:
- El ácido lipoteicoico (LTA) se une y activa directamente el NLRP6.
- La activación de NLRP6 conduce al reclutamiento de caspasa-11 y caspasa-1, promoviendo la maduración de IL-1β e IL-18.
- Los ratones Nlrp6-/- y Casp11-/- presentan una susceptibilidad reducida a la infección por L. monocytogenes, con cargas patógenas más bajas y una producción de IL-18 disminuida.
- La administración de IL-18 restaura la susceptibilidad en ratones Nlrp6-/- o Casp11-/-.
Conclusiones:
- NLRP6 es activado por LTA citosólico, un componente clave de las bacterias Gram-positivas.
- Esta vía LTA-NLRP6-caspase-11 impulsa la producción de IL-18, exacerbando las infecciones bacterianas sistémicas Gram-positivas.
- Los hallazgos revelan una nueva vía de inmunidad innata crucial para la defensa del huésped y el control de patógenos.
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