Constitutive Vagus Nerve Activation Modulates Immune Suppression in Sepsis Survivors

Frontiers in Immunology
Minakshi RanaBetty Diamond

Abstract

Patients surviving a septic episode exhibit persistent immune impairment and increased mortality due to enhanced vulnerability to infections. In the present study, using the cecal ligation and puncture (CLP) model of polymicrobial sepsis, we addressed the hypothesis that altered vagus nerve activity contributes to immune impairment in sepsis survivors. CLP-surviving mice exhibited less TNFα in serum following administration of LPS, a surrogate for an infectious challenge, than control-operated (control) mice. To evaluate the role of the vagus nerve in the diminished response to LPS, mice were subjected to bilateral subdiaphragmatic vagotomy at 2 weeks post-CLP. CLP-surviving vagotomized mice exhibited increased serum and tissue TNFα levels in response to LPS-challenge compared to CLP-surviving, non-vagotomized mice. Moreover, vagus nerve stimulation in control mice diminished the LPS-induced TNFα responses while having no effect in CLP mice, suggesting constitutive activation of vagus nerve signaling in CLP-survivors. The percentage of splenic CD4+ ChAT-EGFP+ T cells that relay vagus signals to macrophages was increased in CLP-survivors compared to control mice, and vagotomy in CLP-survivors resulted in a reduced percentage of ...Continue Reading

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Citations

Jul 18, 2020·Intensive Care Medicine Experimental·Clifford S DeutschmanUNKNOWN Research Committee of the Surviving Sepsis Campaign
Jul 23, 2020·Critical Care Medicine·Clifford S DeutschmanUNKNOWN Research Committee of the Surviving Sepsis Campaign
Jul 20, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Rose A WillemzeWouter J de Jonge
Oct 1, 2019·Current Opinion in Allergy and Clinical Immunology·Mark J PonsfordStephen Jolles
Jan 12, 2020·Journal of Neuroinflammation·Chao RenYong-Ming Yao
Oct 12, 2020·International Forum of Allergy & Rhinology·Jie DengNoam A Cohen
Nov 28, 2020·International Immunopharmacology·Wenting WangHongsheng Ren
Jul 25, 2021·International Journal of Molecular Sciences·Frida Lind-Holm MogensenMaiken Nedergaard

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

Meso Scale Discovery Workbench
ZenBlue
FlowJo
GraphPad Prism

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