Absence of CC chemokine receptor 8 enhances innate immunity during septic peritonitis
Absence of CC chemokine receptor 8 enhances innate immunity during septic peritonitis
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DOI：
10.1096/fj.04-1728fje
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Lira, Sergio A.
中科院分区：
文献类型：
--
作者：
Matsukawa, Akihiro;Kudoh, Shinji;Lira, Sergio A.
有效清除微生物在感染期间的宿主防御中至关重要。在本研究中，我们证明，CC趋化因子受体8（CCR 8）在盲肠结扎穿孔（CLP）诱导的脓毒性腹膜炎过程中扭曲先天免疫反应。在野生型CCR 8 +/+小鼠的CLP期间，CCR 8在驻留的腹腔巨噬细胞中表达并引发白细胞。相对于CCR 8 +/+小鼠，CCR 8 −/−小鼠对CLP诱导的致死性具有抗性，这种抗性与CCR 8 −/−小鼠中细菌清除率增加有关。在体外，来自CCR 8 −/−小鼠的腹腔巨噬细胞，而不是中性粒细胞，表现出相对于CCR 8 +/+小鼠的增强的杀菌活性。在用细菌组分LPS刺激后，超氧化物生成、溶酶体酶释放和一氧化氮生成水平升高，相对于CCR 8 +/+巨噬细胞，在CCR 8 −/−巨噬细胞中检测到用于细菌杀伤的效应分子。此外，CCR 8 −/−巨噬细胞比CCR 8 +/+巨噬细胞产生显著更高水平的已知增强白细胞杀菌活性的几种细胞因子和趋化因子，包括TNF-α，IL-12，巨噬细胞衍生趋化因子（MDC/CCL 22），巨噬细胞炎性蛋白（MIP）-2和KC。总之，这些结果表明，CCR 8可能对宿主防御在脓毒性腹膜炎，提供了一个新的范例CCR 8在先天免疫中的作用产生负面影响。
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‐α, 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.