Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear. ⋯ Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.
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IFN regulatory factor (IRF)3 plays a detrimental role in the cecal ligation and puncture (CLP) mouse model of sepsis. However, it is unclear which pathway activates IRF3 in this context. In this report, we investigate two pathways that activate IRF3: the Stimulator of Interferon Genes (STING) pathway (that senses cytosolic DNA) and the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway (that senses dsRNA and LPS via Toll-like receptor 3 and 4). ⋯ Together, our data demonstrate that both the STING and TRIF pathways can promote sepsis pathogenesis; however, their contribution depends on the severity of the disease model. We show that bacteria are abundant in the peritoneum following both severe and moderate CLP, while cell-free DNA is more highly elevated in the serum following severe CLP compared with sham and moderate CLP. Hence, the presence of bacteria and cell-free DNA may explain the variable phenotypes in our severe CLP model (dependent on TRIF and STING) versus our moderate CLP model (dependent on TRIF only).