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Las terapias específicas del genotipo del huésped pueden optimizar la respuesta inflamatoria a las infecciones
David M Tobin1, Francisco J Roca, Sungwhan F Oh
1Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Cell
|February 7, 2012
Resumen
La susceptibilidad a la tuberculosis puede derivarse de una inflamación demasiado pequeña o demasiado grande. Dirigirse a la vía de la leucotrieno A4 hidrolasa (LTA4H) ofrece nuevas terapias dirigidas al huésped para la tuberculosis, dependiendo de los niveles de inflamación.
Área de la Ciencia:
- Inmunología Inmunología.
- Genética La genética.
- Microbiología Microbiología.
Sus antecedentes:
- La susceptibilidad a la tuberculosis a menudo está relacionada con la respuesta inmune.
- La inflamación juega un papel complejo en el control de las infecciones micobacterianas.
Objetivo del estudio:
- Investigar el doble papel de la inflamación en la susceptibilidad a la tuberculosis.
- Para identificar objetivos moleculares para terapias dirigidas al huésped.
Principales métodos:
- Se utilizaron modelos de pez cebra de la infección por Mycobacterium marinum.
- Analizó el locus de leucotrieno A4 hidrolasa (LTA4H) y su papel en la inflamación.
- Investigó los polimorfismos humanos de LTA4H en pacientes con meningitis tuberculosa.
Principales resultados:
- Se encontró que tanto la inflamación inadecuada como la excesiva contribuyen a la susceptibilidad.
- Identificó dos vías inflamatorias distintas que involucran lipoxinas y leucotrieno B4, convergiendo en la desregulación del TNF.
- Descubrió un polimorfismo promotor de LTA4H asociado con los resultados de los pacientes con meningitis tuberculosa.
Conclusiones:
- Las terapias dirigidas al huésped dirigidas a LTA4H pueden ser beneficiosas para el tratamiento de la tuberculosis.
- Las estrategias terapéuticas deben adaptarse en función del genotipo LTA4H individual y el estado inflamatorio.
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