Critical Role of NOD2 in Regulating the Immune Response to Staphylococcus aureus
Critical Role of NOD2 in Regulating the Immune Response to Staphylococcus aureus
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DOI：
10.1128/iai.00940-08
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发表时间：
2009-04-01
影响因子：
3.1
通讯作者：
Fowler, Vance G., Jr.
中科院分区：
文献类型：
--
作者：
Deshmukh, Hitesh S.;Hamburger, James B.;Fowler, Vance G., Jr.
NOD2（含有蛋白质 2 的核苷酸结合寡聚结构域）已知参与细菌的宿主识别，尽管其在宿主对金黄色葡萄球菌感染的反应中的作用尚不清楚。 NOD2缺陷型(Nod2(-/-))小鼠和野生型(WT)同窝对照小鼠腹膜内注射金黄色葡萄球菌悬浮液(10(7)个细菌/克体重)，并监测它们的存活率。从Nod2(-/-)和WT小鼠中收获培养的骨髓源性中性粒细胞，并测试细胞因子的产生和吞噬作用。与 WT 小鼠相比，Nod2(-/-) 小鼠明显更容易受到金黄色葡萄球菌感染（中位生存期为 1.5 天 vs > 5 天；P = 0.003），并且具有显着更高的细菌组织负荷。来自Nod2(-/-)和WT小鼠的培养的骨髓源性中性粒细胞具有相似的腹膜中性粒细胞募集和细胞内杀伤水平，但来自Nod2(-/-)小鼠的骨髓源性中性粒细胞内化荧光素标记的金黄色葡萄球菌的能力显着降低。与 WT 小鼠相比，Nod2(-/-) 小鼠血清中 Th1 衍生细胞因子（肿瘤坏死因子 α、γ 干扰素和白细胞介素 2 [IL-2]）水平显着较高，而 Nod2(-/-) 和 WT 小鼠中 Th2 衍生细胞因子（IL-1β、IL-4、IL-6 和 IL-10）水平相似。因此，缺乏 NOD2 的小鼠更容易受到金黄色葡萄球菌的影响。易感性增加的部分原因是中性粒细胞吞噬功能缺陷、Th1 细胞因子血清水平升高以及细菌组织负荷较高。
NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role in the host response to Staphylococcus aureus infection is unknown. NOD2-deficient (Nod2(-/-)) mice and wild-type (WT) littermate controls were injected intraperitoneally with S. aureus suspension (10(7) bacteria/g of body weight), and their survival was monitored. Cultured bone marrow-derived neutrophils were harvested from Nod2(-/-) and WT mice and tested for cytokine production and phagocytosis. Compared to WT mice, Nod2(-/-) mice were significantly more susceptible to S. aureus infection (median survival of 1.5 days versus >5 days; P = 0.003) and had a significantly higher bacterial tissue burden. Cultured bone marrow-derived neutrophils from Nod2(-/-) and WT mice had similar levels of peritoneal neutrophil recruitment and intracellular killing, but bone marrow-derived neutrophils from Nod2(-/-) mice had significantly reduced ability to internalize fluorescein-labeled S. aureus. Nod2(-/-) mice had significantly higher levels of Th1-derived cytokines in serum (tumor necrosis factor alpha, gamma interferon, and interleukin-2 [IL-2]) compared to WT mice, whereas the levels of Th2-derived cytokines (IL-1 beta, IL-4, IL-6, and IL-10) were similar in Nod2(-/-) and WT mice. Thus, mice deficient in NOD2 are more susceptible to S. aureus. Increased susceptibility is due in part to defective neutrophil phagocytosis, elevated serum levels of Th1 cytokines, and a higher bacterial tissue burden.