NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila.
NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila.
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DOI：
10.1002/eji.201040518
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发表时间：
2010-12
影响因子：
5.4
通讯作者：
Hawn, Thomas R.
中科院分区：
文献类型：
--
作者：
Berrington, William R.;Iyer, Ravi;Wells, Richard D.;Smith, Kelly D.;Skerrett, Shawn J.;Hawn, Thomas R.
核苷酸结合寡聚化结构域-1（NOD 1）和核苷酸结合寡聚化结构域-2（NOD 2），检测细菌细胞壁分子的细胞质受体，在肺先天免疫应答中的作用知之甚少。我们确定NOD 1和NOD 2都检测热灭活的军团菌，并使用体外荧光素酶报告系统刺激NF-κB和IFN-β启动子活性。接下来，我们用雾化的嗜肺军团菌感染NOD 1和NOD 2缺陷动物。在感染后3天，与WT对照相比，Nodl-/-小鼠具有受损的细菌清除。此外，在4小时和24小时，Nod 1-/-小鼠的肺泡腔中性粒细胞募集受损。相比之下，在24小时时在Nod 2-/-动物中观察到肺嗜中性粒细胞增加。感染后4小时细胞因子产生的分析显示，与WT动物相比，Nod 1-/-动物中的促炎细胞因子显著减少。相比之下，在Nod 2-/-动物中观察到增加的4小时促炎细胞因子。此外，Nod 1-/-和Nod 2-/-小鼠的肺在24小时时具有显著增加的促炎细胞因子水平，这表明可能对感染的后期阶段具有抑制作用。总之，我们的数据表明，虽然NOD 1和NOD 2都可以检测军团菌，但这些受体调节体内肺部免疫反应的方式不同。
The role of nucleotide-binding oligomerization domain-1 (NOD1) and nucleotide-binding oligomerization domain-2 (NOD2), cytoplasmic receptors which detect bacterial cell wall molecules, in pulmonary innate immune responses is poorly understood. We determined that both NOD1 and NOD2 detect heat-killed Legionella and stimulate NF-κb and IFN-β promoter activity using an in vitro luciferase reporter system. We next infected NOD1- and NOD2-deficient animals with aerosolized Legionella pneumophila. At 3 days post infection, Nod1–/– mice had impaired bacterial clearance compared to WT controls. In addition, at 4 h and 24 h, Nod1–/– mice had impaired neutrophil recruitment to the alveolar space. In contrast, increased lung neutrophils were seen in the Nod2–/– animals at 24 h. Analysis of cytokine production at 4 h post infection revealed a significant decrease in proinflammatory cytokines in the Nod1–/– animals when compared to WT animals. In contrast, increased 4-h proinflammatory cytokines were seen in the Nod2–/– animals. Furthermore, the lungs of both Nod1–/– and Nod2–/– mice had significantly increased pro-inflammatory cytokine levels at 24 h, suggesting possible suppressive roles for later stages of infection. Together, our data suggest that although both NOD1 and NOD2 can detect Legionella, these receptors modulate the in vivo pulmonary immune response differently.
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影响因子：
15.3
作者：
Hawn, TR;Verbon, A;Lettinga, KD;Zhao, LP;Li, SS;Laws, RJ;Skerrett, SJ;Beutler, B;Schroeder, L;Nachman, A;Ozinsky, A;Smith, KD;Aderem, A
通讯作者：
Aderem, A
影响因子：
4.4
作者：
Kim, Yun-Gi;Park, Jong-Hwan;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
4.4
作者：
Lamkanfi, Mohamed;Amer, Amal;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
3.4
作者：
Archer KA;Alexopoulou L;Flavell RA;Roy CR
通讯作者：
Roy CR
影响因子：
4.4
作者：
Frevert, CW;Goodman, RB;Martin, TR
通讯作者：
Martin, TR