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Objetivos de tejidos clave responsables de la letalidad inducida por la toxina del ántrax
Shihui Liu1, Yi Zhang, Mahtab Moayeri
1Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. shliu@niaid.nih.gov
Nature
|September 3, 2013
Resumen
Las toxinas de Bacillus anthracis causan letalidad al dañar distintos tipos de células. La toxina letal del ántrax (LT) ataca las células cardíacas y vasculares, mientras que la toxina del edema (ET) afecta principalmente a las células hepáticas (hepatocitos).
Área de la Ciencia:
- Microbiología Microbiología.
- Toxicología Toxicología.
- Fisiopatología Fisiopatología.
Sus antecedentes:
- Bacillus anthracis causa el ántrax a través de dos exotoxinas: la toxina letal (LT) y la toxina del edema (ET).
- Los objetivos específicos de las células huésped responsables de los efectos letales de estas toxinas siguen sin identificarse.
- La proteína de morfogénesis capilar-2 (CMG2) es un receptor conocido para estas toxinas.
Objetivo del estudio:
- Para dilucidar los tipos de células críticas dirigidas por la toxina letal del ántrax (LT) y la toxina del edema (ET) que conducen a la mortalidad del huésped.
- Investigar el papel del receptor de la toxina del ántrax CMG2 en la mediación de la letalidad inducida por la toxina en diferentes tipos de células.
Principales métodos:
- Generación de ratones CMG2-nulo y CMG2-expresores específicos del tipo de célula.
- Desafiando a estos ratones genéticamente modificados con la toxina letal del ántrax purificada (LT) y la toxina del edema (ET).
- Evaluar la contribución de tipos celulares específicos a la mortalidad inducida por toxinas.
Principales resultados:
- La letalidad de LT implica daño a los cardiomiocitos y las células del músculo liso vascular.
- La letalidad inducida por ET está mediada principalmente a través de su acción sobre los hepatocitos.
- Contrariamente a las hipótesis anteriores, la orientación de las células endoteliales por LT o ET no contribuye significativamente a la mortalidad.
Conclusiones:
- Bacillus anthracis emplea LT y ET para inducir la letalidad del huésped mediante el daño coordinado de distintos sistemas de órganos vitales.
- LT y ET exhiben un tropismo de tipo celular diferencial, apuntando a poblaciones celulares críticas separadas para efectos letales.
- Las células endoteliales no son un objetivo primario para la letalidad inducida por la toxina del ántrax.
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