Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium

Maria J. Fernandez-Cabezudo, Dietrich E. Lorke, Sheikh Azimullah, Milena Mechkarska, Mohammed Y. Hasan, Georg A. Petroianu, Basel K. Al-Ramadi

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The cholinergic nervous system has been demonstrated to attenuate the inflammatory response during sepsis via the inhibitory action of acetylcholine (ACh) on macrophages. These findings were largely based on experimental sepsis models using endotoxin as the inducing agent. Herein, however, we report that the specific inhibition of acetylcholinesterase (AChE) renders animals more resistant to infection by a virulent strain of Salmonella enterica serovar Typhimurium, a Gram-negative enteric pathogen. Inhibition of AChE was induced by a subchronic exposure to paraoxon, a potent anti-cholinesterase metabolite of the organophosphorous compound parathion. Our findings indicate that inhibition of AChE enhanced survival of infected mice in a dose-dependent fashion and this correlated with efficient control of bacterial proliferation in target organs. Immunologically, inhibition of AChE enabled the animals to mount a more effective inflammatory anti-microbial response, and to secrete higher levels of interleukin-12, a key T helper type 1-promoting cytokine. The ACh-induced enhancement in resistance to infection was abrogated by co-administration of an oxime which can reactivate AChE. Hence, in a model of Gram-negative bacterial infection, cholinergic stimulation is shown to enhance the anti-microbial immune response leading to effective control of bacterial proliferation and enhanced animal survival.

Original languageEnglish
Pages (from-to)388-398
Number of pages11
JournalImmunology
Volume130
Issue number3
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Acetylcholine
  • Cholinergic anti-inflammatory pathway
  • Innate immunity
  • Organophosphate
  • Salmonella infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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