Absence of CC chemokine receptor 8 enhances innate immunity during septic peritonitis

• Published in: The FASEB journal Vol. 20; no. 2; pp. 302 - 304
• Main Authors: Matsukawa, Akihiro, Kudoh, Shinji, Sano, Gen-ichiro, Maeda, Takako, Ito, Takaaki, Lukacs, Nicholas W, Hogaboam, Cory M, Kunkel, Steven L, Lira, Sergio A
• Format: Journal Article
• Language: English
• Published: United States 01.02.2006
• Subjects: Animals; Bacterial Infections - immunology; Cells, Cultured; Cytokines - deficiency; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Gene Deletion; Gene Expression Regulation; Immunity, Innate - immunology; Kidney - injuries; Kidney - pathology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Peritonitis - immunology; Phagocytosis; Receptors, CCR8
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.04-1728fje

An effective clearance of microbes is crucial in host defense during infection. In the present study, we demonstrate that CC chemokine receptor 8 (CCR8) skews innate immune response during septic peritonitis induced by cecal ligation and puncture (CLP). CCR8 was expressed in resident peritoneal macrophages and elicited leukocytes during CLP in the wild-type CCR8+/+ mice. CCR8-/- mice were resistant to CLP-induced lethality relative to CCR8+/+ mice, and this resistance was associated with an augmented bacterial clearance in CCR8-/- mice. In vitro, peritoneal macrophages from CCR8-/- mice, but not neutrophils, exhibited enhanced bactericidal activities relative to those from CCR8+/+ mice. Upon stimulation with the bacterial component LPS, elevated levels of superoxide generation, lysosomal enzyme release, and nitric oxide generation, effector molecules for bacterial killing were detected in CCR8-/- macrophages relative to CCR8+/+ macrophages. In addition, CCR8-/- macrophages produced significantly higher levels than CCR8+/+ macrophages of several cytokines and chemokines known to augment bactericidal activities of leukocytes that include TNF-alpha, IL-12, macrophage-derived chemokine (MDC/CCL22), macrophage inflammatory protein (MIP)-2, and KC. Altogether, these results indicate that CCR8 may have a negative impact on host defense during septic peritonitis, providing a new paradigm for the role of CCR8 in innate immunity.