Chitin induces accumulation in tissue of innate immune cells associated with allergy
Chitin induces accumulation in tissue of innate immune cells associated with allergy
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DOI：
10.1038/nature05746
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发表时间：
2007-05-03
期刊：
影响因子：
64.8
通讯作者：
Locksley, Richard M.
中科院分区：
文献类型：
--
作者：
Reese, Tiffany A.;Liang, Hong-Erh;Locksley, Richard M.
过敏性和寄生虫免疫的特征是白细胞介素（IL）-4和IL-13表达细胞（包括T辅助细胞-2、嗜酸性粒细胞和嗜碱性粒细胞）浸润组织（1）。组织巨噬细胞具有独特的表型，称为交替激活的巨噬细胞（2）。关于触发这些宿主反应的因素知之甚少。甲壳素是一种广泛存在的N-乙酰基-β-D-葡糖胺环境生物聚合物，为真菌、甲壳类动物、蠕虫和昆虫提供结构刚性（3）。在这里，我们表明，甲壳素诱导IL-4表达的先天性免疫细胞，包括嗜酸性粒细胞和嗜碱性粒细胞，当给予小鼠组织中的积累。组织浸润不受Toll样受体介导的脂多糖识别缺失的影响，但如果用IL-4和IL-13诱导的哺乳动物几丁质酶AMCase（4）预处理注射的几丁质，或者如果将几丁质注射到过表达AMCase的小鼠中，则不会发生组织浸润。甲壳素介导的替代巨噬细胞激活在体内和生产的白三烯B-4，这是所需的最佳免疫细胞招聘。几丁质是一种识别元件，用于组织渗透的先天细胞参与过敏和蠕虫免疫，这一过程可以负调控脊椎动物几丁质酶。
Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils(1). Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages(2). Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-beta-D-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects(3). Here, we show that chitin induces the accumulation in tissue of IL-4- expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase(4), or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B-4, which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase.