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首页> 外文期刊>Infection and immunity >Toll-Like Receptors 2 and 4 Contribute to Sepsis-Induced Depletion of Spleen Dendritic Cells
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Toll-Like Receptors 2 and 4 Contribute to Sepsis-Induced Depletion of Spleen Dendritic Cells

机译：Toll样受体2和4有助于败血症诱导的脾树突状细胞的消耗。

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Depletion of dendritic cells (DC) in secondary lymphoid organs is a hallmark of sepsis-induced immune dysfunction. In this setting, we investigated if Toll-like receptor (TLR)-dependent signaling might modulate the maturation process and the survival of DC. Using a model of sublethal polymicrobial sepsis induced by cecal ligation and puncture, we investigated the quantitative and functional features of spleen DC in wild-type, TLR2?/?, TLR4?/?, and TLR2?/? TLR4?/? mice. By 24 h, a decrease in the relative percentage of CD11chigh spleen DC occurred in wild-type mice but was prevented in TLR2?/?, TLR4?/?, and TLR2?/? TLR4?/? mice. In wild-type mice, sepsis dramatically affected both CD11c+ CD8α+ and CD11c+ CD8α? subsets. In all three types of knockout mice studied, the CD11c+ CD8α+ subset followed a depletion pattern similar to that for wild-type mice. In contrast, the loss of CD11c+ CD8α? cells was attenuated in TLR2?/? and TLR4?/? mice and completely prevented in TLR2?/? TLR4?/? mice. Accordingly, apoptosis of spleen DC was increased in septic wild-type mice and inhibited in knockout mice. In addition we characterized the functional features of spleen DC obtained from septic mice. As shown by increased expression of major histocompatibility complex class II and CD86, polymicrobial sepsis induced maturation of DC, with subsequent increased capacity to prime T lymphocytes, similarly in wild-type and knockout mice. In response to CpG DNA stimulation, production of interleukin-12 was equally impaired in DC obtained from wild-type and knockout septic mice. In conclusion, although dispensable for the DC maturation process, TLR2 and TLR4 are involved in the mechanisms leading to depletion of spleen DC following polymicrobial sepsis.
机译：继发性淋巴器官中树突状细胞（DC）的耗竭是败血症诱导的免疫功能障碍的标志。在这种情况下，我们调查了Toll样受体（TLR）依赖性信号传导是否会调节DC的成熟过程和存活率。使用盲肠结扎和穿刺诱导的亚致死性微生物败血症模型，研究了野生型脾脏DC，TLR2 ？/？，TLR4 ？/？的脾脏DC的定量和功能特征。 sup>和TLR2 ？/？ TLR4 ？/？小鼠。到24小时，野生型小鼠中CD11c 高脾脏DC的相对百分比降低，但TLR2 α/？，TLR4 α/ ？和TLR2 ？/？ TLR4 ？/？小鼠。在野生型小鼠中，脓毒症显着影响CD11c + CD8α + 和CD11c + CD8α？子集。在所有三种研究的基因敲除小鼠中，CD11c + CD8α + 子集的耗竭模式与野生型小鼠相似。相比之下，在TLR2 ？/？和TLR4 ？/？中CD11c + CD8α？细胞的损失减少了。 >小鼠，并在TLR2 ？/？ TLR4 ？/？小鼠中完全预防。因此，在败血性野生型小鼠中脾DC的凋亡增加，而在敲除小鼠中脾DC的凋亡受到抑制。此外，我们表征了从脓毒症小鼠获得的脾脏DC的功能特征。如主要的组织相容性复合物II类和CD86的表达增加所表明的，与野生型和基因敲除小鼠类似，多菌性败血症诱导DC的成熟，随后引发T淋巴细胞的能力增强。响应CpG DNA刺激，从野生型和基因敲除的败血性小鼠获得的DC中白细胞介素12的产生同样受损。总之，尽管对于DC成熟过程必不可少，但TLR2和TLR4参与了导致微生物败血症后脾脏DC耗竭的机制。

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