The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14
The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14
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DOI：
10.4049/jimmunol.180.2.1158
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发表时间：
2008-01-15
影响因子：
4.4
通讯作者：
Gabay, Cem
中科院分区：
文献类型：
--
作者：
Bas, Sylvette;Lief', Laurence;Gabay, Cem
人类单核/巨噬细胞产生促炎细胞因子的衣原体成分和信号通路尚不清楚。为此，我们测试了沙眼衣原体灭活初等体（EB）以及以下7种Ags诱导人单核/巨噬细胞和THP-1细胞产生促炎细胞因子的能力：纯化的LPS、重组热休克蛋白（rhsp）70、rhsp60、rhsp10、质粒开放阅读框3编码的重组多肽（rpgp3）、重组巨噬细胞感染增强剂（rMip）、重组外膜蛋白2 （rOmp2）。除EB外，rMip诱导IL-1 β、tnf - α、IL-6和IL-8的释放能力最强。通过鲎试剂检测、对多粘菌素B （50 μ g/ml）不敏感以及不同的血清需求，可以发现rMip的促炎活性与大肠杆菌LPS污染无关。我们最近证明Mip是一种暴露在EB表面的“经典”细菌性脂蛋白。抗rMip多克隆抗体的存在显著降低了EB的促炎活性。原生Mip能够诱导TNF-a和IL-8的分泌，而非脂化C20A的rip变体则不能。rMip的促炎活性不受高温或蛋白酶K处理的影响，但被脂肪酶处理大大降低，支持脂质修饰在这一过程中的作用。在CD14的帮助下，刺激通路似乎涉及TLR2/TLR1/TLR6，但不涉及TLR4。这些数据支持Mip脂蛋白在沙眼衣原体诱导的炎症反应发病机制中的作用。
Chlamydiae components and signaling pathway(s) responsible for the production of proinflammatory cytokines by human monocytes/macrophages are not clearly identified. To this aim, Chlamydia trachomatis-inactivated elementary bodies (EB) as well as the following seven individual Ags were tested for their ability to induce the production of proinflammatory cytokines by human monocytes/macrophages and THP-1 cells: purified LPS, recombinant heat shock protein (rhsp)70, rhsp60, rhsp10, recombinant polypeptide encoded by open reading frame 3 of the plasmid (rpgp3), recombinant macrophage infectivity potentiator (rMip), and recombinant outer membrane protein 2 (rOmp2). Aside from EB, rMip displayed the highest ability to induce release of IL-1 beta, TNF-alpha, IL-6, and IL-8. rMip proinflammatory activity could not be attributed to Escherichia coli LPS contamination as determined by the Limulus Amoebocyte lysate assay, insensitivity to polymyxin B (50 mu g/ml), and different serum requirement. We have recently demonstrated that Mip is a "classical" bacterial lipoprotein, exposed at the surface of EB. The proinflammatory activity of EB was significantly attenuated in the presence of polyclonal Ab to rMip. Native Mip was able to induce TNF-a and IL-8 secretion, whereas a nonlipidated C20A rMip variant was not. Proinflammatory activity of rMip was unaffected by heat or proteinase K treatments but was greatly reduced by treatment with lipases, supporting a role of lipid modification in this process. Stimulating pathways appeared to involve TLR2/TLR1/TLR6 with the help of CD14 but not TLR4. These data support a role of Mip lipoprotein in pathogenesis of C. trachomatis-induced inflammatory responses.