Identification of dendritic antigen-presenting cells in the zebrafish
Identification of dendritic antigen-presenting cells in the zebrafish
复制标题
DOI：
10.1073/pnas.1000494107
复制
发表时间：
2010-09-07
影响因子：
11.1
通讯作者：
Traver, David
中科院分区：
文献类型：
--
作者：
Lugo-Villarino, Geanncarlo;Balla, Keir M.;Traver, David
在哺乳动物中，树突状细胞 (DC) 构成先天免疫系统和适应性免疫系统之间的关键纽带。 DC 在各种组织中充当免疫哨兵，在遇到病原体时，吞噬外来抗原并将其运输到次级淋巴组织，刺激抗原特异性 T 淋巴细胞。尽管 DC 在协调哺乳动物免疫反应中至关重要，但它们在非哺乳动物脊椎动物中的存在和功能很大程度上未知。由于硬骨鱼拥有最早可识别的适应性免疫系统之一，因此我们试图鉴定斑马鱼中的抗原呈递细胞 (APC)，以更好地了解 DC 的潜在起源及其与淋巴细胞的进化关系。在这里，我们展示了与哺乳动物 DC 非常相似的斑马鱼 APC 子集的鉴定和表征。稀有 DC 存在于各种成体组织中，并且可通过其与凝集素花生凝集素 (PNA) 的亲和力而富集。我们发现，PNA(hi) 骨髓细胞具有哺乳动物 DC 的经典形态特征，如组织化学和超微结构分析、体内吞噬标记细菌制剂所揭示的，并表现出与 DC 功能和抗原呈递相关的基因表达，包括 il12、MHC II 类不变链 iclp1 和 csf1r。重要的是，我们证明 PNA(hi) 细胞可以以抗原依赖性方式激活 T 淋巴细胞。总之，这些研究表明，从硬骨鱼到哺乳动物，负责抗原呈递的细胞成分都非常保守，并表明斑马鱼可以作为研究 APC 亚群的起源及其作为先天性和适应性免疫系统之间的联系的进化作用的独特模型。
In mammals, dendritic cells (DCs) form the key link between the innate and adaptive immune systems. DCs act as immune sentries in various tissues and, upon encountering pathogen, engulf and traffic foreign antigen to secondary lymphoid tissues, stimulating antigen-specific T lymphocytes. Although DCs are of fundamental importance in orchestrating the mammalian immune response, their presence and function in nonmammalian vertebrates is largely unknown. Because teleosts possess one of the earliest recognizable adaptive immune systems, we sought to identify antigen-presenting cells (APCs) in the zebrafish to better understand the potential origins of DCs and their evolutionary relationship to lymphocytes. Here we present the identification and characterization of a zebrafish APC subset strongly resembling mammalian DCs. Rare DCs are present in various adult tissues, and can be enriched by their affinity for the lectin peanut agglutinin (PNA). We show that PNA(hi) myeloid cells possess the classical morphological features of mammalian DCs as revealed by histochemical and ultrastructural analyses, phagocytose-labeled bacterial preparations in vivo, and exhibit expression of genes associated with DC function and antigen presentation, including il12, MHC class II invariant chain iclp1, and csf1r. Importantly, we show that PNA(hi) cells can activate T lymphocytes in an antigen-dependent manner. Together, these studies suggest that the cellular constituents responsible for antigen presentation are remarkably conserved from teleosts to mammals, and indicate that the zebrafish may serve as a unique model to study the origin of APC subsets and their evolutionary role as the link between the innate and adaptive immune systems.