Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection.
Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection.
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先天感知机制触发各种体液和细胞事件，这些事件对适应性免疫反应至关重要。在这里，我们描述了由疟原虫感染触发的一种先天感知途径，它通过释放Flt3L来调节树突状细胞(DC)的动态平衡和适应性免疫。疟原虫诱导的Flt3L的释放需要Toll样受体的激活和I型干扰素的产生。我们发现I型干扰素支持黄嘌呤脱氢酶的上调，黄嘌呤脱氢酶将感染红细胞中积累的黄嘌呤代谢成尿酸。尿酸晶体触发肥大细胞从预先合成的膜相关前体中释放可溶性Flt3L。在感染过程中，Flt3L优先刺激CD8CD8+/CD103+DC亚群或其BDCA3+人树突状细胞亚群的扩张，并对T细胞的激活程度有显著影响，主要是在CD8+亚群中。我们的发现强调了一种新的机制，它调节DC的动态平衡和T细胞对感染的反应。
Innate sensing mechanisms trigger a variety of humoral and cellular events that are essential to adaptive immune responses. Here we describe an innate sensing pathway triggered by Plasmodium infection that regulates dendritic cell (DC) homeostasis and adaptive immunity via Flt3L release. Plasmodium-induced Flt3L release requires toll-like receptor activation and type I interferon production. We find that type I interferon supports the up-regulation of xanthine dehydrogenase, which metabolizes the xanthine accumulating in infected erythrocytes to uric acid. Uric acid crystals trigger mast cells to release soluble Flt3L from a pre-synthesized membrane-associated precursor. During infection Flt3L preferentially stimulates expansion of the CD8α+/CD103+ DC subset or its BDCA3+ human DC equivalent and has a significant impact on the magnitude of T cell activation, mostly in the CD8+ compartment. Our findings highlight a new mechanism that regulates DC homeostasis and T cell responses to infection.
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DOI：
10.1084/jem.20030107
发表时间：
2003-07-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
D'Amico A;Wu L
通讯作者：
Wu L
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
4.4
作者：
Farrand, Kathryn J.;Dickgreber, Nina;Hermans, Ian F.
通讯作者：
Hermans, Ian F.
DOI：
10.1111/j.1600-6143.2009.02755.x
发表时间：
2009-10
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
de Vries VC;Wasiuk A;Bennett KA;Benson MJ;Elgueta R;Waldschmidt TJ;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
4.4
作者：
Belnoue, E;Kayibanda, M;Rénia, L
通讯作者：
Rénia, L