Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.
Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.
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DOI：
10.1371/journal.pone.0033419
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bont L
中科院分区：
文献类型：
--
作者：
Belderbos ME;Levy O;Stalpers F;Kimpen JL;Meyaard L;Bont L
人类新生儿非常容易受到感染，部分原因可能是先天免疫功能受损。新生儿 Toll 样受体 (TLR) 反应偏向于促炎/Th1 极化细胞因子的产生，但其潜在机制尚不完全明确。在这里，我们证明新生儿血浆极化 TLR4 介导的细胞因子产生。当暴露于脐带血血浆时，与暴露于成人血浆的 MC 相比，单核细胞 (MC) 产生的 TLR4 介导的 IL-12p70 显着降低，IL-10 显着升高。新生儿血浆对 TLR4 介导的 IL-12p70 产生的抑制，但不诱导 TLR4 介导的 IL-10 产生，一直维持到 1 个月大。脐带血浆赋予 TLR3 和 TLR8 激动剂类似的 MC 细胞因子反应模式，显示出对 MyD88 依赖性和 MyD88 独立激动剂的活性。导致脐带血浆 TLR4 介导的 IL-10 产生增加的因子是热不稳定的，在蛋白质耗尽后丢失，且不依赖于脂蛋白结合蛋白 (LBP) 或可溶性 CD14 (sCD14)。脐带血浆抑制 TLR4 介导的 IL-12p70 产生的因素对热失活或蛋白质消耗具有抵抗力，并且不依赖于 IL-10、维生素 D 和前列腺素 E2。总之，人新生儿血浆至少含有两种不同的因子，可抑制 TLR4 介导的 IL-12p70 产生或诱导 IL-10 产生。对这些因素的进一步鉴定将有助于深入了解先天免疫发育的个体发育，并可能确定预防和治疗新生儿感染的新靶标。
Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.
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DOI：
10.4049/jimmunol.0901481
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
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
通讯作者：
Wilson CB
影响因子：
3.7
作者：
Lee, Jamie A.;Spidlen, Josef;Boyce, Keith;Cai, Jennifer;Crosbie, Nicholas;Dalphin, Mark;Furlong, Jeff;Gasparetto, Maura.;Goldberg, Michael;Goralczyk, Elizabeth M.;Hyun, Bill;Jansen, Kirstin;Kollmann, Tobias;Kong, Megan;Leif, Robert;McWeeney, Shannon;Moloshok, Thomas D.;Moore, Wayne;Nolan, Garry;Nolan, John;Nikolich-Zugich, Janko;Parrish, David;Purcell, Barclay;Qian, Yu;Selvaraj, Biruntha;Smith, Clayton;Tchuvatkina, Olga;Wertheimer, Anne;WilkinSon, Peter;Wilson, Christopher;Wood, James;Zigon, Robert;Scheuermann, Richard H.;Brinkman, Ryan R.
通讯作者：
Brinkman, Ryan R.
DOI：
10.1016/j.clim.2009.07.003
发表时间：
2009-11
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Belderbos ME;van Bleek GM;Levy O;Blanken MO;Houben ML;Schuijff L;Kimpen JL;Bont L
通讯作者：
Bont L
影响因子：
2.5
作者：
Firth, Matthew A.;Shewen, Patricia E.;Hodgins, Douglas C.
通讯作者：
Hodgins, Douglas C.
影响因子：
20.3
作者：
Levy, Ofer;Suter, Eugenie E.;Wessels, Michael R.
通讯作者：
Wessels, Michael R.