Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock.
Science
; 341(6151): 1250-3, 2013 Sep 13.
Article
em En
| MEDLINE
| ID: mdl-24031018
ABSTRACT
Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and specifically defends against bacterial pathogens that invade the cytosol. During endotoxemia, however, excessive caspase-11 activation causes shock. We report that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected, providing a mechanism of evasion for cytosol-invasive Francisella. Priming the caspase-11 pathway in vivo resulted in extreme sensitivity to subsequent LPS challenge in both wild-type and Tlr4-deficient mice, whereas Casp11-deficient mice were relatively resistant. Together, our data reveal a new pathway for detecting cytoplasmic LPS.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Caspases
/
Receptor 4 Toll-Like
/
Lipídeo A
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2013
Tipo de documento:
Article