In vivo exposure of murine dendritic cell and macrophage bone marrow progenitors to the phosphorylcholine-containing filarial nematode glycoprotein ES-62 polarizes their differentiation to an anti-inflammatory phenotype
In vivo exposure of murine dendritic cell and macrophage bone marrow progenitors to the phosphorylcholine-containing filarial nematode glycoprotein ES-62 polarizes their differentiation to an anti-inflammatory phenotype
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DOI：
10.1111/j.1365-2567.2004.01993.x
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发表时间：
2004-12-01
期刊：
影响因子：
6.4
通讯作者：
Harnett, W
中科院分区：
文献类型：
--
作者：
Goodridge, HS;Marshall, FA;Harnett, W
我们先前已经在体外研究中表明，丝虫线虫含磷酸胆碱（PC）的糖蛋白ES-62促进小鼠树突状细胞（DC）表型，诱导T辅助细胞2型（Th 2）的反应。我们现在表明，除了直接引发Th 2应答外，ES-62还可以抑制脂多糖引起的促炎性DC应答。此外，我们还证明，小鼠树突状细胞和巨噬细胞衍生自体外骨髓细胞暴露在体内ES-62释放从渗透泵是低反应的后续刺激脂多糖。这些作用可以通过暴露于与不相关蛋白质缀合的ES-62的PC部分而在很大程度上模拟。据我们所知，我们提供的数据是第一个表明确定的病原体产物可以调节体内免疫系统骨髓细胞的发育途径。这一发现可能对使用病原体产品或其衍生物进行免疫治疗具有重要意义。
We have previously shown in an in vitro study that the filarial nematode phosphorylcholine (PC)-containing glycoprotein ES-62 promotes a murine dendritic cell (DC) phenotype that induces T helper type 2 (Th2) responses. We now show that, in addition to directly priming Th2 responses, ES-62 can act to dampen down the pro-inflammatory DC responses elicited by lipopolysaccharide. Furthermore, we also demonstrate that murine DCs and macrophages derived ex vivo from bone marrow cells exposed in vivo to ES-62 by release from osmotic pumps are hyporesponsive to subsequent stimulation with lipopolysaccharide. These effects can be largely mimicked by exposure to the PC moiety of ES-62 conjugated to an irrelevant protein. The data we provide are, as far as we aware, the first to show that a defined pathogen product can modulate the developmental pathway of bone marrow cells of the immune system in vivo. Such a finding could have important implications for the use of pathogen products or their derivatives for immunotherapy.