Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis
Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis
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DOI：
10.1038/ni861
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发表时间：
2002-12-01
影响因子：
30.5
通讯作者：
Kaye, PM
中科院分区：
文献类型：
--
作者：
Ato, M;Stäger, S;Kaye, PM
树突状细胞（DC）和T细胞之间的相互作用对于细胞介导的免疫的产生是必不可少的。在这里，我们表明，从小鼠与慢性杜氏利什曼原虫感染的树突状细胞不能从边缘区迁移到动脉周围区域的脾脏。基质细胞较少，这与CCL21和CCL19表达的丧失有关。残余的基质细胞和内皮细胞产生足够的CCL 21来指导从幼稚小鼠转移的DC的迁移。然而，来自感染小鼠的DCs在幼稚受体和体外对CCL21和CCL19的应答中均具有受损的迁移。缺陷定位是由于肿瘤坏死因子依赖性，白细胞介素10介导的抑制CCR7的表达。有效的免疫治疗是用表达CCR7的DC实现的，而不需要鉴定保护性利什曼原虫抗原。因此，缺陷性DC迁移在该疾病的发病机制中起主要作用，并且免疫抑制至少部分地通过DC和T细胞的空间分离介导。
Interaction between dendritic cells (DCs) and T cells is essential for the generation of cell-mediated immunity. Here we show that DCs from mice with chronic Leishmania donovani infection fail to migrate from the marginal zone to the periarteriolar region of the spleen. Stromal cells were fewer, which was associated with loss of CCL21 and CCL19 expression. The residual stromal cells and endothelium produced sufficient CCL21 to direct the migration of DCs transferred from naive mice. However, DCs from infected mice had impaired migration both in naive recipients and in vitro, in response to CCL21 and CCL19. Defective localization was attributable to tumor necrosis factor-dependent, interleukin 10-mediated inhibition of CCR7 expression. Effective immunotherapy was achieved with CCR7-expressing DCs, without the need to identify protective Leishmania antigens. Thus defective DC migration plays a major role in the pathogenesis of this disease and the immunosuppression is mediated, at least in part, through the spatial segregation of DCs and T cells.