Multiplex Analysis of Toll-Like Receptor-Stimulated Neonatal Cytokine Response
Multiplex Analysis of Toll-Like Receptor-Stimulated Neonatal Cytokine Response
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DOI：
10.1159/000255165
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发表时间：
2010-01-01
期刊：
影响因子：
2.5
通讯作者：
Hill, Harry R.
中科院分区：
文献类型：
--
作者：
Caron, Justin E.;La Pine, Timothy R.;Hill, Harry R.
背景：人类新生儿对细菌感染的易感性增加尚不完全清楚。 Toll 样受体 (TLR) 已被认为是对先天免疫反应至关重要的模式识别受体。然而，新生儿的 TLR 功能仍未完全确定。目的：检查脐带血与成人血相比对 TLR-1-6 刺激的调节和促炎细胞因子反应。方法：我们用每个 TLR 1-6 的配体刺激脐带血，并将这些反应与成人对照进行比较。使用以下 TLR 配体：Pam3CSK4（TLR-1 和 2）、酵母聚糖（TLR-2 和 6）、poly I:C (TLR-3)、LPS (TLR-4) 和鞭毛蛋白 (TLR-5)。细胞因子的产生是通过利用多分析物技术内部开发的测定法来测量的。结果：与成人血液相比，TLR-1-6 刺激在脐带血中产生更高浓度的促炎细胞因子（IL-1β、IL-6 和 IL-8），但 TLR-4 刺激的 TNF-α 产生除外，其在脐带血中 (319 pg/ml) 显着低于成人血液 (645 pg/ml；p = 0.027)。相反，与成人血液相比，TLR-1-6刺激导致脐带血中Th1和Th2细胞因子的浓度降低，并且IL-12（TLR 1/2、2/6、3和4）、IL-13（TLR-1-6）和IL-10（TLR-4）的产生显着减少。结论：与成人血液相比，TLR 刺激后脐带血中调节性 Th1 和 Th2 细胞因子的产生减少。相比之下，除了 TLR-4 诱导的 TNF-α 产生外，新生儿中 TLR 刺激的促炎细胞因子的产生明显高于成人。人类新生儿对细菌感染的易感性增加可能与 TLR 反应异常有关，其中促炎性增强和调节性细胞因子产生减少。版权所有 (C) 2009 S. Karger AG，巴塞尔
Background: The human neonate's increased susceptibility to bacterial infections is not completely understood. Toll-like receptors (TLRs) have been recognized as pattern-recognition receptors critical to the innate immune response. TLR function in neonates, however, remains incompletely defined. Objective: To examine regulatory and proinflammatory cytokine responses to TLR-1-6 stimulation of cord blood compared to adult blood. Methods: We stimulated cord blood with ligands for each of TLRs 1-6 and compared these responses to adult controls. The following TLR ligands were utilized: Pam3CSK4 (TLR-1 and 2), zymosan (TLR-2 and 6), poly I: C (TLR-3), LPS (TLR-4), and flagellin (TLR-5). Cytokine production was measured with an assay developed in-house utilizing multi-analyte technology. Results: TLR-1-6 stimulation produced higher concentrations of proinflammatory cytokines (IL-1 beta, IL-6, and IL-8) in cord blood compared to adult blood, with the exception of TLR-4-stimulated TNF-alpha production, which was significantly lower in cord blood (319 pg/ml) compared to adult blood (645 pg/ml; p = 0.027). In contrast, TLR-1-6 stimulation resulted in decreased concentrations of Th1 and Th2 cytokines in cord blood compared to adult blood, with significantly diminished production of IL-12 (TLRs 1/2, 2/6, 3 and 4), IL-13 (TLR-1-6), and IL-10 (TLR-4). Conclusion: Cord blood production of regulatory Th1 and Th2 cytokines following TLR stimulation is decreased compared to that of adult blood. In contrast, TLR-stimulated proinflammatory cytokine production was markedly higher in neonates than in adults, with the exception of TLR-4-induced TNF-alpha production. The human neonate's increased susceptibility to bacterial infections may be related to abnormal TLR responsiveness, with enhanced proinflammatory and decreased regulatory cytokine production. Copyright (C) 2009 S. Karger AG, Basel