首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells
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Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells

机译:啮齿类柠檬酸杆菌感染过程中排结肠淋巴结中浆细胞样树突状细胞的激活涉及与常规树突状细胞不同的病原体传感和炎性途径

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Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11c(high)CD103(high)) DC and plasmacytoid (plasmacytoid DC Ag-1(high)B220(+)CD11c(int)) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis.
机译:树突状细胞(DC)承担启动抗微生物免疫所必需的适应性免疫反应的主要责任。在小肠中,传入淋巴管将Ags和微生物信号传递到肠系膜淋巴结(LNs),以诱导针对源自小肠的微生物和食物Ags的适应性免疫反应。直到最近,才研究大肠是被同一淋巴系统覆盖还是代表其自身的淋巴区室。我们确定了三个与小肠LN不同的小肠系膜LN,这些小肠LN专门从结肠排出淋巴液,并研究了DC对其中附着和消灭的病原鼠杆状杆菌的DC反应。在稳态条件下常规(CD11c(高)CD103(高))DC和浆细胞样(浆细胞样DC Ag-1(高)B220(+)CD11c(int))DC(pDC)群体的转录谱分析显示了不同组的活性在小肠和结肠引流性淋巴结中这两个DC亚组中的基因啮齿类念珠菌激活DC,尤其是在排结肠LN中,与常规DC相比,pDC中的基因表达变化更为深刻。在pDC中上调最多的基因包括C型凝集素受体CLEC4E,IL-1R(IL-1R1和-2),促炎细胞因子(IL-1a和IL-6)和TLR6。我们的结果表明,就引流LN而言,结肠免疫监视与小肠免疫监视不同,并且将pDC识别为结肠炎症和/或微生物营养不良的活跃前哨。

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