Schistosome larvae stimulate macrophage cytokine production through TLR4-dependent and -independent pathways.
Schistosome larvae stimulate macrophage cytokine production through TLR4-dependent and -independent pathways.
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DOI：
10.1093/intimm/dxh319
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发表时间：
2005-11
影响因子：
4.4
通讯作者：
Mountford AP
中科院分区：
文献类型：
--
作者：
Jenkins SJ;Hewitson JP;Ferret-Bernard S;Mountford AP
哺乳动物宿主暴露于感染性曼氏血吸虫幼虫会引起皮肤急性炎症反应，并激活包括巨噬细胞在内的几种细胞类型的先天免疫反应。使用体外巨噬细胞活化模型，我们发现，巨噬细胞体幼虫具有直接刺激巯基乙酸盐诱导的巨噬细胞（tMφ）和IFNγ激活的tMφ在体外产生几种细胞因子，包括IL-6，IL-12 p40和IL-10的分子。寄生虫衍生的分子富集在寄生虫转化后释放的物质[0 - 3-h释放的幼虫制剂（0- 3 HRP）]中，但不在整个幼虫的可溶性制剂中。在多粘菌素B的存在下维持细胞因子的产生，证实污染的内毒素不是原因。来自C3 H/HeJ小鼠的细胞的IL-12 p40和IL-10产生低得多，其具有缺陷的Toll样受体4（TLR 4），但IL-6产生不受影响。使用TLR 4-/-小鼠的实验证实，tMφ响应0- 3 HRP产生IL-12 p40部分依赖于功能性TLR 4，而IL-6的产生完全独立。相比之下，MyD 88-/-小鼠的tMφ不能分泌IL-12 p40或IL-6，强调TLR信号传导在巨噬细胞响应0- 3 HRP刺激产生细胞因子中的关键作用。最后，我们表明0- 3 HRP的聚糖组分是最佳细胞因子产生所需的，因为0- 3 HRP的蛋白酶处理对IL-12 p40的产生没有影响，对IL-6只有轻微的影响，而偏高碘酸钠处理几乎完全消除了两种细胞因子的产生。
Exposure of the mammalian host to infective larvae of Schistosoma mansoni causes an acute inflammatory response in the skin and the activation of several cell types of the innate immune response including macrophages. Using an in vitro model of macrophage activation, we show that schistosome larvae possess molecules that directly stimulate both thioglycollate-elicited macrophages (tMφ) and IFNγ-activated tMφ in vitro to produce several cytokines including IL-6, IL-12p40 and IL-10. The parasite-derived molecules are enriched within the material released by the parasite following transformation [0- to 3-h released larval preparation (0-3hRP)] but not within soluble preparations of whole larvae. Cytokine production was maintained in the presence of polymyxin B, confirming that contaminating endotoxin was not responsible. IL-12p40 and IL-10 production was much lower by cells from C3H/HeJ mice, which have defective Toll-like receptor 4 (TLR4), but IL-6 production was unaffected. Experiments using TLR4-/- mice confirmed that IL-12p40 production by tMφ in response to 0-3hRP was partly dependent upon functional TLR4, whereas IL-6 production was entirely independent. In contrast, tMφ from MyD88-/- mice failed to secrete either IL-12p40 or IL-6, underlining a pivotal role of TLR signalling in cytokine production by macrophages in response to stimulation with 0-3hRP. Finally, we show that glycan components of 0-3hRP are required for optimal cytokine production since protease treatment of 0-3hRP had no effect on IL-12p40 production and only a slight effect on IL-6, while sodium meta-periodate treatment almost completely abolished production of both cytokines.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
影响因子：
4.3
作者：
Huang, HH;Tsai, PL;Khoo, KH
通讯作者：
Khoo, KH
影响因子：
3.1
作者：
Luchi, M;Morrison, DC
通讯作者：
Morrison, DC
影响因子：
4.4
作者：
Kaisho, T;Hoshino, K;Akira, S
通讯作者：
Akira, S
影响因子：
4.8
作者：
Aksoy, E;Zouain, CS;Trottein, F
通讯作者：
Trottein, F