The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes.
The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes.
复制标题
DOI：
10.1016/j.immuni.2011.04.013
复制
发表时间：
2011-05-27
期刊：
影响因子：
32.4
通讯作者：
Núñez G
中科院分区：
文献类型：
--
作者：
Kim YG;Kamada N;Shaw MH;Warner N;Chen GY;Franchi L;Núñez G
细胞内传感器Nod 2响应于细菌而被激活，并且这种响应的损害与克罗恩病有关。然而，Nod 2在宿主防御中的功能仍然知之甚少。我们发现，Nod 2 −/−小鼠表现出对啮齿类柠檬酸杆菌（Citrobacter rodentium）的肠道清除受损，这是一种肠道细菌，模拟人类感染致病性大肠杆菌。增加的细菌负荷之前，减少CCL 2趋化因子的生产，炎症单核细胞的招聘，并在肠道中的Th 1细胞反应。结肠基质细胞，而不是上皮细胞或常驻CD 11b+吞噬细胞，产生CCL 2响应C。啮齿类，这是受损的Nod 2 −/−细胞。与常驻吞噬细胞不同，炎性单核细胞产生IL-12，这是一种诱导病原体清除所需的适应性免疫的细胞因子。Ly 6Chi单核细胞的连续转移恢复了感染Ccr 2 −/−小鼠中病原体的清除。因此，Nod 2介导炎症单核细胞的CCL 2-CCR 2依赖性募集，这在促进肠道细菌根除中很重要。
The intracellular sensor Nod2 is activated in response to bacteria, and the impairment of this response is linked to Crohn’s disease. However, the function of Nod2 in host defense remains poorly understood. We found that Nod2−/− mice exhibited impaired intestinal clearance of Citrobacter rodentium, an enteric bacterium that models human infection by pathogenic Escherichia coli. The increased bacterial burden was preceded by reduced CCL2 chemokine production, inflammatory monocyte recruitment, and Th1 cell responses in the intestine. Colonic stromal cells, but not epithelial cells or resident CD11b+ phagocytic cells, produced CCL2 in response to C. rodentium, which was impaired in Nod2−/− cells. Unlike resident phagocytic cells, inflammatory monocytes produced IL-12, a cytokine that induces adaptive immunity required for pathogen clearance. Adoptive transfer of Ly6Chi monocytes restored the clearance of the pathogen in infected Ccr2−/− mice. Thus, Nod2 mediates CCL2-CCR2-dependent recruitment of inflammatory monocytes, which is important in promoting bacterial eradication in the intestine.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
5.4
作者：
Monteleone, Ivan;Platt, Andrew M.;Mowat, Allan McI.
通讯作者：
Mowat, Allan McI.
影响因子：
4.3
作者：
Cruickshank, Sheena M.;Wakenshaw, Louise;Carding, Simon R.
通讯作者：
Carding, Simon R.
影响因子：
30.5
作者：
Denning, Timothy L.;Wang, Yi-Chong;Pulendran, Bali
通讯作者：
Pulendran, Bali
影响因子：
29.4
作者：
Lawrance, IC;Wu, F;Chakravarti, S
通讯作者：
Chakravarti, S