TRIF signaling is required for caspase-11-dependent immune responses and lethality in sepsis.
Mol Med
; 24(1): 66, 2018 12 27.
Article
em En
| MEDLINE
| ID: mdl-30587103
ABSTRACT
BACKGROUND:
Caspase-11, a cytosolic receptor of bacterial endotoxin (lipopolysaccharide LPS), mediates immune responses and lethality in endotoxemia and experimental sepsis. However, the upstream pathways that regulate caspase-11 activation in endotoxemia and sepsis are not fully understood. The aim of this study is to test whether TIR-domain-containing adapter-inducing interferon-ß (TRIF) signaling is critical for caspase-11-dependent immune responses and lethality in endotoxemia.METHODS:
Mice of indicated genotypes were subjected to endotoxemia or cecum ligation and puncture (CLP) and monitored daily by signs of a moribund state for lethality. Serum interleukin (IL)-1α, IL-1ß, IL-6 and tumor necrosis factor (TNF) were measured by ELISA. Data were analyzed by using student's t-test or one-way ANOVA followed by post-hoc Bonferroni test. Survival data were analyzed by using the log-rank test.RESULTS:
Blockade of type 1 interferon signaling or genetic deletion of TRIF or guanylate-binding proteins (GBPs) prevented caspase-11-dependent immune responses, organ injury and lethality in endotoxemia and experimental sepsis. In vitro, deletion of GBPs blocked cytosolic LPS-induced caspase-11 activation in mouse macrophages.CONCLUSIONS:
These findings demonstrate that TRIF signaling is required for caspase-11-dependent immune responses and lethality in endotoxemia and sepsis, and provide novel mechanistic insights into how LPS induces caspase-11 activation during bacterial infection.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endotoxemia
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Caspases
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Proteínas Adaptadoras de Transporte Vesicular
Limite:
Animals
Idioma:
En
Revista:
Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2018
Tipo de documento:
Article