Toll-like receptor 2 controls the gamma interferon response to Francisella tularensis by mouse liver lymphocytes
Toll-like receptor 2 controls the gamma interferon response to Francisella tularensis by mouse liver lymphocytes
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DOI：
10.1128/iai.00561-07
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发表时间：
2007-11-01
影响因子：
3.1
通讯作者：
Parmely, Michael J.
中科院分区：
文献类型：
--
作者：
Hong, Kee-Jong;Wickstrum, Jason R.;Parmely, Michael J.
γ干扰素（IFN-γ）的产生是对土拉弗朗西斯菌的保护性先天免疫应答的关键步骤。肝脏中的自然杀伤细胞和T细胞是原发性F.土拉菌感染，白细胞介素-12（IL-12）似乎是肝IFN-γ表达的必需共激活细胞因子。本研究旨在确定巨噬细胞（M phi）或树突状细胞（DC）是否在体外为肝脏IFN-γ反应提供共激活信号，IL-12是否介导这些作用，以及Toll样受体（TLR）信号传导是否对诱导这种共刺激活性至关重要。骨髓来源的M phi和DC均显著增强F.体外土拉菌感染的肝淋巴细胞。而两种细胞均能产生IL-12 p40。tularensis攻击后，只有DC分泌大量IL-12 p70。来自IL-12 p35缺陷型和TLR 2缺陷型小鼠的DC均未能产生IL-12 p70，并且不会共刺激肝淋巴细胞响应活F产生IFN-γ。土拉热菌相反，TLR 2缺陷小鼠与野生型辅助细胞共培养的肝淋巴细胞产生的IFN-γ水平与野生型肝淋巴细胞相当。这些发现表明TLR 2控制肝淋巴细胞对F的IFN-γ应答。土拉菌通过调节DC IL-12的产生。而M phi也可诱导F. tularensis，他们这样做的方式不太依赖TLR 2。
The production of gamma interferon (IFN-gamma) is a key step in the protective innate immune response to Francisella tularensis. Natural killer cells and T cells in the liver are important sources of this cytokine during primary F. tularensis infections, and interleukin-12 (IL-12) appears to be an essential coactivating cytokine for hepatic IFN-gamma expression. The present study was undertaken to determine whether or not macrophages (M phi) or dendritic cells (DC) provide coactivating signals for the liver IFN-gamma response in vitro, whether IL-12 mediates these effects, and whether Toll-like receptor (TLR) signaling is essential to induce this costimulatory activity. Both bone marrow-derived M phi and DC significantly augmented the IFN-gamma response of F. tularensis-challenged liver lymphocytes in vitro. While both cell types produced IL-12p40 in response to F. tularensis challenge, only DC secreted large quantities of IL-12p70. DC from both IL-12p35-deficient and TLR2-deficient mice failed to produce IL-12p70 and did not costimulate liver lymphocytes for IFN-gamma production in response to viable F. tularensis organisms. Conversely, liver lymphocytes from TLR2-deficient mice cocultured with,wild-type accessory cells produced IFN-gamma at levels comparable to those for wild-type hepatic lymphocytes. These findings indicate that TLR2 controls hepatic lymphocyte IFN-gamma responses to F. tularensis by regulating DC IL-12 production. While M phi also coinduced hepatic IFN-gamma production in response to F. tularensis, they did so in a fashion less dependent on TLR2.