Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii
Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii
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DOI：
10.4049/jimmunol.164.9.4826
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发表时间：
2000-05-01
影响因子：
4.4
通讯作者：
Reichmann, G
中科院分区：
文献类型：
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作者：
Fischer, HG;Bonifas, U;Reichmann, G
在小鼠慢性感染弓形虫期间，在脑单核细胞中检测到 IL-12p40、CD86 和钾通道 Kv1.3 的基因信息，表明中枢神经系统中存在树突状细胞 (DC)。一致的是，带有 DC 标记 CD11c 和 33D1 的细胞仅定位于受感染大脑的炎症部位。分离出的 CD11c(+) 脑细胞数量不断增加，直至炎症达到顶峰。细胞通过共表达 33D1 和 F4/80、少量 DEC-205 且无 CD8 α 表现出髓样 DC 的表面表型。 MHC II 类、CD40、CD54、CD80 和 CD86 的高水平表达表明，这些脑 DC 是成熟的，它们以非常低的 APC/T 细胞比率触发 Ag 特异性和初级同种异体 T 细胞反应。在来自脑炎脑的单核细胞中，DC是IL-12的主要产生者，在体外获得了CNS祖细胞依赖寄生虫发育DC的证据：用弓形虫接种原代脑细胞培养物后，出现分泌IL-12的树状细胞，并表达DC标记基因。不同的刺激引发脑 DC 的产生和成熟：中和寄生虫诱导的 GM-CSF 可防止树状细胞的生长，并同时释放 IL-12，IL-12 的产生被外部 IFN-γ 上调，但通过抑制寄生虫复制而停止。一致地，从 GM-CSF 处理的脑细胞培养物中分离出的 DC 仅通过暴露于寄生虫裂解物而被激活以分泌 IL-12。总之，这些结果证明了弓形虫诱导的 CNS 中 DC 的扩张和功能成熟，因此强调了可能有助于宿主长期反应的机制。
During chronic infection of mice,vith Toxoplasma gondii, gene message for IL-12p40, CD86, and the potassium channel Kv1.3 was detected in brain mononuclear cells, suggesting the presence of dendritic cells (DC) in the CNS. Consistently, cells bearing the DC markers CD11c and 33D1 mere localized at inflammatory sites in the infected brain. The number of isolated CD11c(+) brain cells increased until peak inflammation. The cells exhibited the surface phenotype of myeloid DC by coexpressing 33D1 and F4/80, little DEC-205, and no CD8 alpha. These brain DC were mature, as indicated by high-level expression of MHC class II, CD40, CD54, CD80, and CD86, They triggered Ag-specific and primary allogeneic T cell responses at very low APC/T cell ratios. Among mononuclear cells from encephalitic brain, DC were the main producers of IL-12, Evidence for a parasite-dependent development of DC from CNS progenitors was obtained in vitro: after inoculation of primary brain cell culture with T. gondii, IL-12-secreting dendriform cells emerged, and DC marker genes were expressed. Different stimuli elicited the generation and maturation of brain DC: neutralization of parasite-induced GM-CSF prevented outgrowth of dendriform cells and concomitant release of IL-12, IL-12 production was up-regulated by external IFN-gamma but was stopped by inhibiting parasite replication. Consistently, DC isolated from GM-CSF-treated brain cell culture mere activated to secrete IL-12 by exposure to parasite lysate. In sum, these results demonstrate T. gondii-induced expansion and functional maturation of DC in the CNS and, thus, highlight a mechanism that may contribute to the chronicity of the host response.