The chemokine receptor CCR6 is an important component of the innate immune response.
In our initial studies we found that naïve CCR6-deficient (CCR6(-/-)) C57BL/6 mice possessed significantly lower number of both F4/80(+) macrophages and dendritic cells (DC), but higher number of B cells in the peritoneal cavity, as compared to naïve wild type (WT) controls. Furthermore, peritoneal macrophages isolated from CCR6(-/-) mice expressed significantly lower levels of inflammatory cytokines and nitric oxide following lipopolysaccharide (LPS)stimulation, as compared to WT macrophages. In a severe experimental peritonitis model induced by cecal ligation and puncture (CLP), CCR6(-/-) mice were protected when compared with WT controls. At 24 h following the induction of peritonitis, CCR6(-/-) mice exhibited significantly lower levels of inflammatory cytokines/chemokines in both the peritoneal cavity and blood. Interestingly, DC recruitment into the peritoneal cavity was impaired in CCR6(-/-) mice during the evolution of CLP-induced peritonitis. Peritoneal macrophages isolated from surviving CCR6(-/-) mice 3 days after CLP-induced peritonitis exhibited an enhanced LPS response compared with similarly treated WT peritoneal macrophages. These data illustrate that CCR6 deficiency alters the innate response via attenuating the hyperactive local and systemic inflammatory response during CLP-induced peritonitis.
Wen
Haitao
H
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Hogaboam
Cory M
CM
Lukacs
Nicholas W
NW
Cook
Donald N
DN
Lira
Sergio A
SA
Kunkel
Steven L
SL
D000818:Animals; D002432:Cecum / Q000378:metabolism / Q000601:surgery; D002465:Cell Movement; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000166:cytology; D010538:Peritonitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015996:Survival Rate
C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016207:Cytokines; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine