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

Background. The efferent vagus nerve can inhibit inflammation via interaction between acetylcholine and alpha 7 cholinergic receptors. Methods. To determine the role played by alpha 7 receptors in antibacterial defense, peritonitis was induced in alpha 7 receptor-deficient (alpha 7(-/-)) and wild-type (WT) mice by intraperitoneal injection with Escherichia coli. Results. At 20 h after infection, virtually all alpha 7(-/-) 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 alpha 7(-/-) 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 alpha 7(-/-) and WT mice, the former mouse strain showed a more robust influx of neutrophils into the peritoneal cavity. Conclusions. Deficiency of the alpha 7 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 alpha 7 receptors in the host defense against bacteria.