Deficiency of α7 cholinergic receptors facilitates bacterial clearance in Escherichia coli peritonitis

Abstract

Background. The efferent vagus nerve can inhibit inflammation via interaction between acetylcholine and α7 cholinergic receptors. Methods. To determine the role played by α7 receptors in antibacterial defense, peritonitis was induced in α7 receptor-deficient (α7-/-) and wild-type (WT) mice by intraperitoneal injection with Escherichia coli. Results. At 20 h after infection, virtually all α7-/- mice had cleared the infection from their peritoneal cavities and had sterile blood cultures, whereas WT mice had high bacterial loads at the primary site of infection and were bacteremic. In addition, bacterial burdens in liver, spleen, kidneys, and lungs were much lower in α7-/- mice, and these animals displayed a diminished inflammatory response, as reflected by a reduced number of infiltrating neutrophils in peritoneal lavage fluid and lower circulating cytokine levels. At 2 h after infection, however, when bacterial loads were still similar in α7-/- and WT mice, the former mouse strain showed a more robust influx of neutrophils into the peritoneal cavity. Conclusions. Deficiency of the α7 receptor is associated with an accelerated clearance of E. coli after intraperitoneal infection, preceded by a faster recruitment of neutrophils. These data provide the first evidence for a detrimental role of α7 receptors in the host defense against bacteria. © 2008 by the Infectious Diseases Society of America. All rights reserved.