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感染杜氏利什曼原虫的易感和抗性小鼠的病变及淋巴结中受感染细胞的无鞭毛体负荷和细胞表面表型。

Amastigote load and cell surface phenotype of infected cells from lesions and lymph nodes of susceptible and resistant mice infected with Leishmania major.

作者信息

Muraille Eric, De Trez Carl, Pajak Bernard, Torrentera Fabiola Aguilar, De Baetselier Patrick, Leo Oberdan, Carlier Yves

机构信息

Laboratory of Parasitology, Université Libre de Bruxelles, Erasme, Brussels, Belgium.

出版信息

Infect Immun. 2003 May;71(5):2704-15. doi: 10.1128/IAI.71.5.2704-2715.2003.

Abstract

Cells of the dendritic cell (DC) lineage, by their unique ability to stimulate naive T cells, may be of crucial importance in the development of protective immune responses to Leishmania parasites. The aim of this study was to compare the impact of L. major infection on DCs in BALB/c (susceptible, developing Th2 responses), C57BL/6 (resistant, developing Th1 responses), and tumor necrosis factor (TNF)(-/-) C57BL/6 mice (susceptible, developing delayed and reduced Th1 responses). We analyzed by immunohistochemistry the phenotype of infected cells in vivo. Granulocytes (GR1(+)) and macrophages (CD11b(+)) appear as the mainly infected cells in primary lesions. In contrast, cells expressing CD11c, a DC specific marker, are the most frequently infected cells in draining lymph nodes of all mice tested. These infected CD11c(+) cells harbored a particular morphology and cell surface phenotype in infected C57BL/6 and BALB/c mice. CD11c(+) infected cells from C57BL/6 and TNF(-/-) C57BL/6 mice displayed a weak parasitic load and a dendritic morphology and frequently expressed CD11b or F4/80 myeloid differentiation markers. In contrast, some CD11c(+) infected cells from BALB/c mice were multinucleated giant cells. Giant cells presented a dramatic accumulation of parasites and differentiation markers were not detectable at their surface. In all mice, lymph node CD11c(+) infected cells expressed a low major histocompatibility complex II level and no detectable CD86 expression. Our results suggest that infected CD11c(+) DC-like cells might constitute a reservoir of parasites in lymph nodes.

摘要

树突状细胞(DC)谱系的细胞具有刺激初始T细胞的独特能力,在针对利什曼原虫的保护性免疫反应的发展中可能至关重要。本研究的目的是比较硕大利什曼原虫感染对BALB/c小鼠(易感,产生Th2反应)、C57BL/6小鼠(抗性,产生Th1反应)和肿瘤坏死因子(TNF)(-/-)C57BL/6小鼠(易感,产生延迟且减弱的Th1反应)中DC的影响。我们通过免疫组织化学分析了体内感染细胞的表型。粒细胞(GR1(+))和巨噬细胞(CD11b(+))是原发性病变中主要被感染的细胞。相比之下,表达DC特异性标志物CD11c的细胞是所有测试小鼠引流淋巴结中最常被感染的细胞。在感染的C57BL/6和BALB/c小鼠中,这些被感染的CD11c(+)细胞具有特定的形态和细胞表面表型。来自C57BL/6和TNF(-/-) C57BL/6小鼠的CD11c(+)感染细胞寄生虫负荷较低,呈树突状形态,并经常表达CD11b或F4/80髓系分化标志物。相比之下,来自BALB/c小鼠的一些CD11c(+)感染细胞是多核巨细胞。巨细胞中寄生虫大量聚集,其表面未检测到分化标志物。在所有小鼠中,淋巴结CD11c(+)感染细胞主要组织相容性复合体II水平较低,未检测到CD86表达。我们的结果表明,被感染的CD11c(+) DC样细胞可能构成淋巴结中寄生虫的储存库。

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