Neonatal innate TLR-mediated responses are distinct from those of adults.
Neonatal innate TLR-mediated responses are distinct from those of adults.
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DOI：
10.4049/jimmunol.0901481
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发表时间：
2009-12-01
期刊：
影响因子：
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通讯作者：
Wilson CB
中科院分区：
文献类型：
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作者：
Kollmann TR;Crabtree J;Rein-Weston A;Blimkie D;Thommai F;Wang XY;Lavoie PM;Furlong J;Fortuno ES 3rd;Hajjar AM;Hawkins NR;Self SG;Wilson CB
人类新生儿和婴儿对各种微生物的感染非常敏感。这种易感性被认为反映了先天免疫和适应性免疫与成人的差异，但这些差异的性质并不完全。先天性免疫应答在整合来自Toll样受体（TLR）和其他环境传感器的信息后指导随后的适应性免疫应答。我们开始提供一个全面的分析，定义人类新生儿和成人之间的TLR结扎反应的差异。在对大多数TLR配体的应答中，新生儿先天性免疫细胞，包括单核细胞、常规和浆细胞样树突状细胞（分别为cDC和pDC），产生较少的IL-12 p70和IFN-α（并因此诱导较少的IFN-γ），中度较少的TNF-α，但与成人细胞一样多或甚至更多的IL-1β、IL-6、IL-23和IL-10。在单细胞水平，新生儿先天细胞通常不太能够同时产生多种细胞因子，即，功能较少。总的来说，我们的数据表明，新生儿与成人白色血细胞TLR介导的应答支持Th 17和Th 2型免疫的能力强（如果不是增强的话），这促进了对细胞外病原体的防御，但支持Th 1型应答的能力降低，这促进了对细胞内病原体的防御。
The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from Toll-like receptors (TLRs) and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes, conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively), produced less IL-12p70 and IFN-α (and consequently induced less IFN-γ), moderately less TNF-α, but as much or even more IL-1β, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs. the adult white blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.