Poly(I:C) Priming Exacerbates Cecal Ligation and Puncture-Induced Polymicrobial Sepsis in Mice

In this study, we examined the role of TLR3 priming in the immunopathology of sepsis using cecal-ligation and puncture (CLP) model of sepsis in mice. Mice injected with vehicle or poly(I:C) were subjected to sham or CLP surgery and various parameters of sepsis, including mortality, inflammation, and bacterial clearance were assessed. Poly(I:C) pre-treatment significantly enhanced mortality in mice subjected to CLP. Consistent with this, inflammatory cytokines including TNF α, IL-12p40, IFNγ, and MCP-1 were enhanced both systemically and locally in the poly(I:C)-treated group compared to the vehicle control. In addition, bacterial load was significantly higher in the poly(I:C)-treated septic mice. These changes were associated with reduced macrophage activation (but not neutrophils) in the peritoneal cavity of poly(I:C) pre-treated mice compared to vehicle pre-treatment. Together our results demonstrate that poly(I:C) priming in sepsis is likely to be detrimental to the host due to effects on systemic inflammatory cytokines and bacterial clearance.

Source: Inflammation - January 10, 2018 Category: Allergy & Immunology Source Type: research