Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: Evidence for a negative signal delivered through the mannose receptor
Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: Evidence for a negative signal delivered through the mannose receptor
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DOI：
10.4049/jimmunol.166.12.7477
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发表时间：
2001-06-15
影响因子：
4.4
通讯作者：
Puzo, G
中科院分区：
文献类型：
--
作者：
Nigou, J;Zelle-Rieser, C;Puzo, G
IL-12是指导I型Th细胞发育的关键细胞因子，对于根除细胞内病原体（如结核分枝杆菌）至关重要。在这里，我们报道了来自牛分枝杆菌卡介苗和结核分枝杆菌的甘露糖盖脂arabinomarmans （manlam）以剂量依赖性的方式抑制lps诱导的人树突状细胞产生IL-12。抑制活性因甘露糖帽或GPI酰基残基的丢失而消失。甘露聚糖是甘露糖受体（MR）的配体，也是MR特异性的单抗，也抑制了lps诱导的树突状细胞产生IL-12。我们的研究结果表明，manlam可能作为毒力因子，通过抑制IL-12反应，促进牛分枝杆菌卡尔梅特- guerin和结核分枝杆菌在吞噬细胞内的持久性。我们的数据还表明，manlam对MR的作用产生负信号，干扰toll样受体传递的lps诱导的正信号。
IL-12 is a key cytokine in directing the development of type I Th cells, which are critical to eradicate intracellular pathogens such as Mycobacterium tuberculosis. Here, we report that mannose-capped lipoarabinomarmans (ManLAMs) from Mycobacterium bovis bacillus Calmette-Guerin and Mycobacterium tuberculosis inhibited, in a dose-dependant manner, the LPS-induced IL-12 production by human dendritic cells. The inhibitory activity was abolished by the loss of the mannose caps or the GPI acyl residues. Mannan, which is a ligand for the mannose receptor (MR) as well as an mAb specific for the MR, also inhibited the LPS-Induced IL-12 production by dendritic cells. Our results indicate that ManLAMs may act as virulence factors that contribute to the persistence of M. bovis bacillus Calmette-Guerin and M. tuberculosis within phagocytic cells by suppressing IL-12 responses. Our data also suggest that engagement of the MR by ManLAMs delivers a negative signal that interferes with the LPS-induced positive signals delivered by the Toll-like receptors.