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

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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.

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Acknowledgements

We gratefully acknowledge the support from NIH (grants HL095637, AI099404, and AR056680 to N.P.). We thank the University lab animal resources for taking excellent care of our animals and the Histopathology laboratory for their excellent service.

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Authors and Affiliations

  1. Department of Physiology, Michigan State University, 567 Wilson Road, #2201 Biomedical Physical Sci. Bldg, East Lansing, MI, 48824, USA

    Deepika Sharma, Ankit Malik, Nandakumar Packiriswamy, Michael D. Steury & Narayanan Parameswaran

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  1. Deepika Sharma
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  2. Ankit Malik
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  3. Nandakumar Packiriswamy
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  4. Michael D. Steury
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  5. Narayanan Parameswaran
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Correspondence to Narayanan Parameswaran.

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Sharma, D., Malik, A., Packiriswamy, N. et al. Poly(I:C) Priming Exacerbates Cecal Ligation and Puncture-Induced Polymicrobial Sepsis in Mice. Inflammation 41, 328–336 (2018). https://doi.org/10.1007/s10753-017-0690-6

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