Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
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DOI：
10.1038/nm1720
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发表时间：
2008-03-01
期刊：
影响因子：
82.9
通讯作者：
Ouyang, Wenjun
中科院分区：
文献类型：
--
作者：
Zheng, Yan;Valdez, Patricia A.;Ouyang, Wenjun
通过附着和消除（A/E）细菌病原体（如大肠杆菌O 157：H7）的感染对公共卫生构成严重威胁。利用小鼠A/E病原体，啮齿柠檬酸杆菌，我们表明白细胞介素-22（IL-22）在宿主防御C.啮齿动物。IL-22敲除小鼠的感染导致肠上皮损伤、全身细菌负荷和死亡率增加。我们还发现，IL-23在C.啮齿动物感染，和适应性免疫是不是必不可少的IL-22在这个模型中的保护作用。相反，IL-22是结肠上皮细胞中直接诱导Reg家族的抗微生物蛋白（包括RegIII β和RegIII γ）所必需的。外源性小鼠或人RegIII γ显著改善C.啮齿类感染总之，我们的数据确定了IL-22在调节针对A/E细菌病原体的早期防御机制中的新的先天免疫功能。
Infections by attaching and effacing (A/E) bacterial pathogens, such as Escherichia coli O157:H7, pose a serious threat to public health. Using a mouse A/E pathogen, Citrobacter rodentium, we show that interleukin-22 (IL-22) has a crucial role in the early phase of host defense against C. rodentium. Infection of IL-22 knockout mice results in increased intestinal epithelial damage, systemic bacterial burden and mortality. We also find that IL-23 is required for the early induction of IL-22 during C. rodentium infection, and adaptive immunity is not essential for the protective role of IL-22 in this model. Instead, IL-22 is required for the direct induction of the Reg family of antimicrobial proteins, including RegIII beta and RegIII gamma, in colonic epithelial cells. Exogenous mouse or human RegIII gamma substantially improves survival of IL-22 knockout mice after C. rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens.