Divergent effects of mycobacterial cell wall glycolipids on maturation and function of human monocyte-derived dendritic cells.
Divergent effects of mycobacterial cell wall glycolipids on maturation and function of human monocyte-derived dendritic cells.
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DOI：
10.1371/journal.pone.0042515
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hamasur B
中科院分区：
文献类型：
--
作者：
Mazurek J;Ignatowicz L;Kallenius G;Svenson SB;Pawlowski A;Hamasur B
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）能够逃避免疫防御，并且可以在感染的宿主中持续数年、数十年甚至终身。结核分枝杆菌细胞壁成分可能通过调节几种关键类型的免疫细胞而促成这种持久性。树突状细胞（Dendritic cells，DCs）是最强的抗原提呈细胞，通过连接先天性免疫系统和适应性免疫系统，在感染后的初始免疫应答中起着至关重要的作用。我们研究了两种主要的分枝杆菌细胞壁相关类型的糖脂，甘露糖帽脂阿拉伯甘露聚糖（ManLAM）和磷脂酰肌醇甘露糖苷（PIM）纯化的结核分枝杆菌菌株H37 Rv和牛分枝杆菌，对成熟和细胞因子的不成熟的人单核细胞衍生的DC的影响。来自Mtb H37 Rv的ManLAM刺激促炎细胞因子TNF、IL-12和IL-6的释放以及共刺激分子（CD 80、CD 86）和抗原呈递分子（MHC II类）的表达。来自M.牛也诱导TNF、IL-12和IL-6，但水平显著较低。重要的是，虽然发现ManLAM增加LPS诱导的DC成熟和促炎细胞因子产生，但添加来自Mtb H37 Rv和M. Bovis强烈地降低了这种刺激作用。这些结果表明，分枝杆菌细胞壁含有糖脂性质的大分子，其能够诱导对人DC的强烈和不同的作用;即，虽然ManLAM是免疫刺激性的，但PIM充当DC细胞因子应答的强效抑制剂。因此，PIM可能是重要的结核病相关的毒力因子，有助于结核病的发病机制。这些发现也可能有助于理解早期关于不同ManLAM制剂所产生的免疫调节作用的一些相互矛盾的报告。
Mycobacterium tuberculosis (Mtb) is able to evade the immune defenses and may persist for years, decades and even lifelong in the infected host. Mtb cell wall components may contribute to such persistence by modulating several pivotal types of immune cells. Dendritic cells (DCs) are the most potent antigen-presenting cells and hence play a crucial role in the initial immune response to infections by connecting the innate with the adaptive immune system. We investigated the effects of two of the major mycobacterial cell wall-associated types of glycolipids, mannose-capped lipoarabinomannan (ManLAM) and phosphatidylinositol mannosides (PIMs) purified from the Mtb strains H37Rv and Mycobacterium bovis, on the maturation and cytokine profiles of immature human monocyte-derived DCs. ManLAM from Mtb H37Rv stimulated the release of pro-inflammatory cytokines TNF, IL-12, and IL-6 and expression of co-stimulatory (CD80, CD86) and antigen-presenting molecules (MHC class II). ManLAM from M. bovis also induced TNF, IL-12 and IL-6 but at significantly lower levels. Importantly, while ManLAM was found to augment LPS-induced DC maturation and pro-inflammatory cytokine production, addition of PIMs from both Mtb H37Rv and M. bovis strongly reduced this stimulatory effect. These results indicate that the mycobacterial cell wall contains macromolecules of glycolipid nature which are able to induce strong and divergent effects on human DCs; i.e while ManLAM is immune-stimulatory, PIMs act as powerful inhibitors of DC cytokine responses. Thus PIMs may be important Mtb-associated virulence factors contributing to the pathogenesis of tuberculosis disease. These findings may also aid in the understanding of some earlier conflicting reports on the immunomodulatory effects exerted by different ManLAM preparations.
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影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
4.4
作者：
Andersen, Claire S.;Agger, Else Marie;Andersen, Peter
通讯作者：
Andersen, Peter
影响因子：
3.1
作者：
CHAN, J;FAN, X;BLOOM, BR
通讯作者：
BLOOM, BR
影响因子：
4.8
作者：
Bulut, Y;Michelsen, KS;Arditi, M
通讯作者：
Arditi, M
影响因子：
4.4
作者：
Geurtsen, Jeroen;Chedammi, Sunita;Appelmelk, Ben J.
通讯作者：
Appelmelk, Ben J.