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

Abstract

Sepsis continues to be a major healthcare issue with one of the highest mortality rates in intensive care units. Toll-like receptors are pattern recognition receptors that are intricately involved in the pathogenesis of sepsis. TLR3 is a major receptor for double-stranded RNA and is largely associated with immunity to viral infection. 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 TNFα, 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.

• Authors: Deepika Sharma, Ankit Malik, Nandakumar Packiriswamy, Michael D Steury, Narayanan Parameswaran
• Journal: Inflammation (Inflammation) Vol. 41 Issue 1 Pg. 328-336 (Feb 2018) ISSN: 1573-2576 [Electronic] United States
• PMID: 29127663 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Inflammation Mediators
• Poly I-C

Topics

• Animals
• Bacterial Load
• Cecum (microbiology, surgery)
• Cytokines (immunology, metabolism)
• Disease Models, Animal
• Disease Progression
• Inflammation Mediators (immunology, metabolism)
• Ligation
• Macrophage Activation (drug effects)
• Macrophages (drug effects, immunology, metabolism, microbiology)
• Mice, Inbred C57BL
• Neutrophils (drug effects, immunology, metabolism, microbiology)
• Poly I-C (toxicity)
• Punctures
• Sepsis (chemically induced, immunology, metabolism, microbiology)
• Time Factors