[HTML][HTML] TRIF signaling is required for caspase-11-dependent immune responses and lethality in sepsis
Y Tang, R Zhang, Q Xue, R Meng, X Wang, Y Yang… - Molecular …, 2018 - Springer
Y Tang, R Zhang, Q Xue, R Meng, X Wang, Y Yang, L Xie, X Xiao, TR Billiar, B Lu
Molecular Medicine, 2018•SpringerBackground 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-β (TRIF) signaling is critical for caspase-11-
dependent immune responses and lethality in endotoxemia. Methods Mice of indicated …
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-β (TRIF) signaling is critical for caspase-11-
dependent immune responses and lethality in endotoxemia. Methods Mice of indicated …
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-β (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-1β, 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.
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