Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development
Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development
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DOI：
10.1073/pnas.1711530114
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发表时间：
2017-11-21
影响因子：
11.1
通讯作者：
Gilmore, Thomas D.
中科院分区：
文献类型：
--
作者：
Brennan, Joseph J.;Messerschmidt, Jonathan L.;Gilmore, Thomas D.
从昆虫到脊椎动物。Toll样受体（TLR）是激活下游途径的主要病原体检测器，特别是那些指导先天免疫效应基因表达的下游途径。TLR在许多物种的发育中也有作用。海葵Nematostella vectensis是一个有用的刺胞动物模型，研究TLR信号的起源，因为它的基因组编码一个单一的TLR和许多下游信号组分的同源物，包括NF-κ B途径。我们描述了单个N。vectensis TLR（Nv-TLR），并证明其可以激活人细胞中的经典NF-κ B信号传导。此外，我们还发现Nv-TLR的细胞内Toll/IL-1受体（TIR）结构域可以与人TLR接头蛋白MAL和MYD 88相互作用。我们证明，珊瑚病原体溶珊瑚弧菌导致一个快速致命的疾病，在N。vectensis，并且热灭活的解珊瑚弧菌和细菌鞭毛蛋白可以激活人细胞中重建的Nv-TLR-至-NF-κ B途径。通过海葵的免疫染色，我们发现Nv-TLR在一个亚群的刺胞中表达，并且许多表达Nv-TLR的细胞也表达Nv-NF-κ B。此外，线虫体是线虫属特异性的多细胞结构，表达Nv-TLR和许多先天免疫途径同源物，并且可以吞噬溶珊瑚弧菌。Morpholino敲低表明Nv-TLR在早期胚胎发育过程中也具有重要作用。我们对这种原始TLR的表征和对N. vectensis揭示了古老的TLR功能，为研究刺胞动物疾病和免疫的分子基础提供了一个模型。
In organisms from insects to vertebrates. Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-kappa B pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-kappa B signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR-to-NF-kappa B pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR- expressing cells also express Nv-NF-kappa B. Additionally, the nematosome, which is a Nematostella-specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus. Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity.