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- Title
TRIF signaling is required for caspase-11-dependent immune responses and lethality in sepsis.
- Authors
Tang, Yiting; Zhang, Rui; Xue, Qianqian; Meng, Ran; Wang, Xiangyu; Yang, Yanliang; Xie, Lingli; Xiao, Xianzhong; Billiar, Timothy R.; Lu, Ben
- 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-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.
- Subjects
ENDOTOXEMIA; IMMUNE response; SEPSIS; IMMUNOLOGY; BACTEREMIA
- Publication
Molecular Medicine, 2018, Vol 24, Issue 1, pN.PAG
- ISSN
1076-1551
- Publication type
Article
- DOI
10.1186/s10020-018-0065-y