The sympathetic nervous system drives hyperinflammatory responses to Clostridioides difficile infection.

Cell Rep Med

Neuroscience Graduate Program, University of Virginia Health System, Charlottesville, VA 22908, USA; Departments of Medicine, Pathology, Microbiology, Immunology and Cancer Biology, University of Virginia Health System, Charlottesville, VA 22908, USA; Division of Infectious Disease and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. Electronic address:

Published: October 2024

AI Article Synopsis

  • * This study investigates how the sympathetic nervous system (SNS) influences the severity of CDI using mouse models and treatments that inhibit SNS activity.
  • * The findings show that blocking certain SNS pathways significantly reduces illness severity and mortality in CDI, suggesting that targeting these neural systems could be a potential new treatment approach.

Article Abstract

Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infections in the United States, known for triggering severe disease by hyperactivation of the host response. In this study, we determine the impact of the sympathetic nervous system (SNS) on CDI disease severity. Mouse models of CDI are administered inhibitors of SNS activity prior to CDI. Chemical sympathectomy or pharmacological inhibition of norepinephrine synthesis greatly reduces mortality and disease severity in the CDI model. Pharmacological blockade or genetic ablation of the alpha 2 adrenergic receptor ameliorates intestinal inflammation, disease severity, and mortality rate. These results underscore the role of the SNS and the alpha 2 adrenergic receptor in CDI pathogenesis and suggest that targeting neural systems could be a promising approach to therapy in severe disease.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513855PMC
http://dx.doi.org/10.1016/j.xcrm.2024.101771DOI Listing

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