Toll-like receptors are part of the innate immune defense system of sponges (demospongiae: Porifera).
Toll-like receptors are part of the innate immune defense system of sponges (demospongiae: Porifera).
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DOI：
10.1093/molbev/msl208
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发表时间：
2006-12
影响因子：
10.7
通讯作者：
M. Wiens;M. Korzhev;S. Perović-Ottstadt;B. Luthringer;David Brandt;S. Klein;W. Müller
中科院分区：
文献类型：
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作者：
M. Wiens;M. Korzhev;S. Perović-Ottstadt;B. Luthringer;David Brandt;S. Klein;W. Müller
在进化过程中，随着多细胞动物的出现，需要抵御威胁动物身体完整性的外来生物。在参与识别微生物入侵者的许多不同受体中，toll样受体（TLRs）在介导先天免疫反应中起着重要作用。在结合不同的微生物成分后，tlr激活细胞内信号级联，导致诱导多种抗菌分子的表达。因为海绵（Porifera门）是滤食性动物，它们大量暴露于代表潜在威胁的微生物中。在这里，我们描述了鉴定，克隆，并从3个主要元素的孔虫先天反应（细菌脂肽）的蛋白质序列推断：TLR， IL-1受体相关的激酶-4样蛋白（IRAK-4l），和一个新的效应半胱天冬酶从demosponge亚种软骨。在高等后生动物中，每个分子与其同源物具有显著的序列相似性。在toll/interleukin-1受体/抗性（TLR家族）、Ser/Thr/Tyr激酶结构域（IRAK家族）和CASc （caspase家族）中发现了序列同源性。此外，原位杂交和免疫组织学分析显示，海绵表面上皮层（外表皮和内表皮）中有丰富的SDTLR （TLR）转录本。此外，研究表明，无论是否用合成三酰基脂肽Pam(3)Cys-Ser-(Lys)(4)处理，SDTLR和SDIRAK-4 like （IRAK）都是组成性表达的(4)。相反，SDCASL （caspase）的表达高度受Pam(3)Cys-Ser-(Lys)(4)诱导。然而，在应用之前用重组TLR阻断脂肽完全阻止了这种多孔蛋白半胱天冬酶的诱导表达。这些结果强调，在系统发育上最古老的现存后生动物门已经提供了后生动物抗微生物宿主防御系统的信号通路。
During evolution and with the emergence of multicellular animals, the need arose to ward off foreign organisms that threaten the integrity of the animal body. Among many different receptors that participate in the recognition of microbial invaders, toll-like receptors (TLRs) play an essential role in mediating the innate immune response. After binding distinct microbial components, TLRs activate intracellular signaling cascades that result in an induced expression of diverse antimicrobial molecules. Because sponges (phylum Porifera) are filter feeders, they are abundantly exposed to microorganisms that represent a potential threat. Here, we describe the identification, cloning, and deduced protein sequence from 3 major elements of the poriferan innate response (to bacterial lipopeptides): the TLR, the IL-1 receptor-associated kinase-4-like protein (IRAK-4l), and a novel effector caspase from the demosponge Suberites domuncula. Each molecule shares significant sequence similarity with its homologues in higher Metazoa. Sequence homologies were found in particular within the family-specific domains toll/interleukin-1 receptor/resistance (TLR family), Ser/Thr/Tyr kinase domain (IRAK family), and CASc (caspase family). In addition, in situ hybridization and immunohistological analyses revealed an abundance of SDTLR (TLR) transcripts in epithelial layers of the sponge surface (exopinacoderm and endopinacoderm). Furthermore, it is shown that both SDTLR and SDIRAK-4 like (IRAK) are expressed constitutively, regardless of treatment with synthetic triacyl lipopeptide Pam(3)Cys-Ser-(Lys)(4). In contrast, SDCASL (caspase) expression is highly Pam(3)Cys-Ser-(Lys)(4) inducible. However, blocking of the lipopeptide with recombinant TLR prior to its application completely prevented the induced expression of this poriferan caspase. These results underscore that the phylogenetically oldest extant metazoan phylum is provided already with the signaling pathways of the antimicrobial host-defense system of Metazoa.