Chitin Particles Are Multifaceted Immune Adjuvants
Chitin Particles Are Multifaceted Immune Adjuvants
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DOI：
10.1164/rccm.200912-1877oc
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发表时间：
2010-12-15
影响因子：
24.7
通讯作者：
Elias, Jack A.
中科院分区：
文献类型：
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作者：
Da Silva, Carla A.;Pochard, Pierre;Elias, Jack A.
原理：甲壳素是真菌、昆虫、过敏原和寄生虫中普遍存在的一种多糖，在感染部位释放。目的：我们假设几丁质是一种重要的获得性免疫佐剂。方法：给小鼠注射卵清蛋白和几丁质的溶液。测量和主要结果：我们用体内和体外的方法来表征几丁质片段诱导针对卵蛋白的适应性免疫反应的能力，并将这些反应与氢氧化铝(明胶)诱导的反应进行比较。在体内，卵清蛋白攻击引起了富含嗜酸性粒细胞的肺部炎症反应，Th2细胞因子的产生，IgE的诱导，以及用卵清蛋白+甲壳素或卵清蛋白+明胶致敏的小鼠的粘液化生。Toll样受体-2、MyD88和IL-17A在甲壳素诱导的反应中起关键作用，MyD88和IL-17A在明矾诱导的反应中起关键作用。体外，用卵清蛋白和甲壳素致敏的小鼠的CD4(+)T细胞与卵清蛋白刺激的骨髓来源的树突状细胞孵育。在这些实验中，对CD4(+)T细胞的增殖、IL-5、IL-13、干扰素-γ和IL-17A的产生进行了评价。Toll样受体-2、MyD88和IL-17A在甲壳素的这些体外佐剂特性中起着关键作用。TLR-2是细胞增殖所必需的，而IL-17和TLR-2则是细胞因子形成所必需的。IL-17A还抑制适应性Th1应答的产生。结论：甲壳素是一种有效的多方面佐剂，可诱导适应性Th2、Th1和Th17免疫应答。他们还证明了甲壳素的佐剂特性是由一条途径(S)介导的，该途径涉及TLR-2、MyD88和IL-17A，并受其调节。
Rationale: Chitin is a ubiquitous polysaccharide in fungi, insects, allergens, and parasites that is released at sites of infection. Its role in the generation of tissue inflammation, however, is not fully understood.Objectives: We hypothesized that chitin is an important adjuvant for adaptive immunity.Methods: Mice were injected with a solution of ovalbumin and chitin.Measurements and Main Results: We used in vivo and ex vivo/in vitro approaches to characterize the ability of chitin fragments to foster adaptive immune responses against ovalbumin and compared these responses to those induced by aluminum hydroxide (alum). In vivo, ovalbumin challenge caused an eosinophil-rich pulmonary inflammatory response, Th2 cytokine elaboration, IgE induction, and mucus metaplasia in mice that had been sensitized with ovalbumin plus chitin or ovalbumin plus alum. Toll-like receptor-2, MyD88, and IL-17A played critical roles in the chitin-induced responses, and MyD88 and IL-17A played critical roles in the alum-induced responses. In vitro, CD4(+) T cells from mice sensitized with ovalbumin plus chitin were incubated with ovalbumin-stimulated bone marrow derived dendritic cells. In these experiments, CD4(+) T-cell proliferation, IL-5, IL-13, IFN-gamma, and IL-17A production were appreciated. Toll-like receptor-2, MyD88, and IL-17A played critical roles in these in vitro adjuvant properties of chitin. TLR-2 was required for cell proliferation, whereas IL-17 and TLR-2 were required for cytokine elaboration. IL-17A also inhibited the generation of adaptive Th1 responses.Conclusions: These studies demonstrate that chitin is a potent multifaceted adjuvant that induces adaptive Th2, Th1, and Th17 immune responses. They also demonstrate that the adjuvant properties of chitin are mediated by a pathway(s) that involves and is regulated by TLR-2, MyD88, and IL-17A.