Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis.
Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis.
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DOI：
10.4049/jimmunol.0902009
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发表时间：
2010-06-01
期刊：
影响因子：
--
通讯作者：
Finkelman FD
中科院分区：
文献类型：
--
作者：
Herbert DR;Orekov T;Roloson A;Ilies M;Perkins C;O'Brien W;Cederbaum S;Christianson DW;Zimmermann N;Rothenberg ME;Finkelman FD
另外激活的巨噬细胞通过目前尚不清楚的机制预防感染人类寄生虫曼氏血吸虫的小鼠中由虫卵引起的致死性肠道病变。这项研究表明，精氨酸酶I（Arg I），IL-4和IL-13诱导的交替激活的巨噬细胞的主要产物，防止恶病质，嗜中性粒细胞，急性血吸虫病和内毒素血症。特别地，Arg I阳性巨噬细胞促进TGF-β产生和Foxp 3表达，抑制Ag特异性T细胞增殖，并限制Th 17分化。S.与感染的野生型骨髓嵌合体相比，曼氏感染的Arg I缺陷型骨髓嵌合体在回肠内产生显著的虫卵积累，但粪便虫卵排泄受损。精氨酸缺乏骨髓嵌合体肠内虫卵积聚与肠出血和经典巨噬细胞活化相关分子的产生有关（增加IL-6、NO和IL-12/IL-23 p40的产生），但是尽管NO合酶-2的抑制具有边际效应，IL-12/IL-23 p40中和消除了恶病质和肠道炎症，并减少了肠道内的卵子数量。因此，巨噬细胞来源的Arg I通过抑制IL-12/IL-23 p40的产生和维持肠粘膜内Treg/Th 17平衡来保护宿主免受急性血吸虫病期间由虫卵引起的过度组织损伤。
Alternatively activated macrophages prevent lethal intestinal pathology caused by worm ova in mice infected with the human parasite Schistosoma mansoni through mechanisms that are currently unclear. This study demonstrates that arginase I (Arg I), a major product of IL-4– and IL-13–induced alternatively activated macrophages, prevents cachexia, neutrophilia, and endotoxemia during acute schistosomiasis. Specifically, Arg I-positive macrophages promote TGF-β production and Foxp3 expression, suppress Ag-specific T cell proliferation, and limit Th17 differentiation. S. mansoni-infected Arg I-deficient bone marrow chimeras develop a marked accumulation of worm ova within the ileum but impaired fecal egg excretion compared with infected wild-type bone marrow chimeras. Worm ova accumulation in the intestines of Arg I-deficient bone marrow chimeras was associated with intestinal hemorrhage and production of molecules associated with classical macrophage activation (increased production of IL-6, NO, and IL-12/IL-23p40), but whereas inhibition of NO synthase-2 has marginal effects, IL-12/IL-23p40 neutralization abrogates both cachexia and intestinal inflammation and reduces the number of ova within the gut. Thus, macrophage-derived Arg I protects hosts against excessive tissue injury caused by worm eggs during acute schistosomiasis by suppressing IL-12/IL-23p40 production and maintaining the Treg/Th17 balance within the intestinal mucosa.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
6.4
作者：
Babu, Subash;Kumaraswami, V.;Nutman, Thomas B.
通讯作者：
Nutman, Thomas B.
影响因子：
--
作者：
Mosser, David M;Zhang, Xia
通讯作者：
Zhang, Xia
DOI：
10.1084/jem.20082048
发表时间：
2009-04-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nair MG;Du Y;Perrigoue JG;Zaph C;Taylor JJ;Goldschmidt M;Swain GP;Yancopoulos GD;Valenzuela DM;Murphy A;Karow M;Stevens S;Pearce EJ;Artis D
通讯作者：
Artis D
影响因子：
4.4
作者：
Hoffmann, KF;Cheever, AW;Wynn, TA
通讯作者：
Wynn, TA