Deficiency of alpha7 cholinergic receptors facilitates bacterial clearance in Escherichia coli peritonitis.
BACKGROUND
The efferent vagus nerve can inhibit inflammation via interaction between acetylcholine and alpha7 cholinergic receptors.


METHODS
To determine the role played by alpha7 receptors in antibacterial defense, peritonitis was induced in alpha7 receptor-deficient (alpha7(-/-)) and wild-type (WT) mice by intraperitoneal injection with Escherichia coli.


RESULTS
At 20 h after infection, virtually all alpha7(-/-) 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 alpha7(-/-) 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 alpha7(-/-) and WT mice, the former mouse strain showed a more robust influx of neutrophils into the peritoneal cavity.


CONCLUSIONS
Deficiency of the alpha7 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 alpha7 receptors in the host defense against bacteria.
Giebelen
Ilona A J
IA
Center for Infection and Immunity Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
Le Moine
Alain
A
van den Pangaart
Petra S
PS
Sadis
Claude
C
Goldman
Michel
M
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000276:immunology; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010537:Peritoneum / Q000382:microbiology; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor