Borrelia burgdorferi elicited-IL-10 suppresses the production of inflammatory mediators, phagocytosis, and expression of co-stimulatory receptors by murine macrophages and/or dendritic cells.
Borrelia burgdorferi elicited-IL-10 suppresses the production of inflammatory mediators, phagocytosis, and expression of co-stimulatory receptors by murine macrophages and/or dendritic cells.
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DOI：
10.1371/journal.pone.0084980
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wooten RM
中科院分区：
文献类型：
--
作者：
Chung Y;Zhang N;Wooten RM
伯氏疏螺旋体是一种由壁虱传播的螺旋体，是莱姆病的病原体。我们以前的研究表明，强毒BB可以有效地促进巨噬细胞产生IL-10(M？S)，而阻断IL-10的产生显著增强细菌的清除。我们推测，皮肤相关的APC类型，如M？S和树突状细胞(DC)是BB反应中产生IL-10的强效细胞，BB可能以自分泌方式抑制对有效清除BB至关重要的APC反应。我们的目标是利用莱姆病的小鼠模型来描述BB诱导的IL-10对哪些APC免疫功能的失调。我们的体外研究表明，两种APC在暴露于BB后都能迅速产生IL-10，这些水平与许多莱姆相关的促炎细胞因子和趋化因子的产生呈负相关，并且来自IL-10-/-小鼠的APC比野生型APC产生更多的这些促炎介质。巨噬细胞吞噬实验结果显示，BB诱导的IL-10水平可抑制M？S对BB的摄取和转运，抑制ROS的产生，但不影响NO的产生；BB诱导的IL-10对DC的吞噬、ROS和NO的产生几乎没有影响。总体而言，BB暴露几乎不会引起S和DC的几个关键表面共刺激标志物的上调，然而，消除BB诱导的IL-10可以显著上调许多这些共刺激受体。这些数据表明，从BB刺激的M？S和DC产生的IL-10导致促炎介质和共刺激分子的产生减少，并抑制吞噬相关事件，而吞噬相关事件对于介导APC的先天和获得性免疫反应是重要的。
Borrelia burgdorferi (Bb) is a tick-borne spirochete that is the causative agent for Lyme disease. Our previous studies indicate that virulent Bb can potently enhance IL-10 production by macrophages (MØs) and that blocking IL-10 production significantly enhances bacterial clearance. We hypothesize that skin-associated APC types, such as MØs and dendritic cells (DCs) are potent producers of IL-10 in response to Bb, which may act in autocrine fashion to suppress APC responses critical for efficient Bb clearance. Our goal is to delineate which APC immune functions are dysregulated by Bb-elicited IL-10 using a murine model of Lyme disease. Our in vitro studies indicated that both APCs rapidly produce IL-10 upon exposure to Bb, that these levels inversely correlate with the production of many Lyme-relevant proinflammatory cytokines and chemokines, and that APCs derived from IL-10-/- mice produced greater amounts of these proinflammatory mediators than wild-type APCs. Phagocytosis assays determined that Bb-elicited IL-10 levels can diminish Bb uptake and trafficking by MØs, suppresses ROS production, but does not affect NO production; Bb-elicited IL-10 had little effect on phagocytosis, ROS, and NO production by DCs. In general, Bb exposure caused little-to-no upregulation of several critical surface co-stimulatory markers by MØs and DCs, however eliminating Bb-elicited IL-10 allowed a significant upregulation in many of these co-stimulatory receptors. These data indicate that IL-10 elicited from Bb-stimulated MØs and DCs results in decreased production of proinflammatory mediators and co-stimulatory molecules, and suppress phagocytosis-associated events that are important for mediating both innate and adaptive immune responses by APCs.
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