Innate immune defense of the sponge Suberites domuncula against bacteria involves a MyD88-dependent signaling pathway -: Induction of a perforin-like molecule
Innate immune defense of the sponge Suberites domuncula against bacteria involves a MyD88-dependent signaling pathway -: Induction of a perforin-like molecule
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DOI：
10.1074/jbc.m504049200
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发表时间：
2005-07-29
影响因子：
4.8
通讯作者：
Müller, WEG
中科院分区：
文献类型：
--
作者：
Wiens, M;Korzhev, M;Müller, WEG
海绵动物（多孔动物门）是最古老的后生动物;作为滤食性动物，它们大量暴露于海洋微生物。在这里，我们提出的数据表明，demosponge Suberites domuncula提供了一个识别系统的革兰氏阴性细菌。脂多糖（LPS）相互作用蛋白被鉴定为海绵细胞表面的受体，其识别细菌内毒素LPS。分离cDNA，并表达蛋白质（M-r 49，937）。在与LPS结合期间，蛋白质二聚化并与MyD 88相互作用，MyD 88也被鉴定和克隆。海绵MyD 88（M-r 28，441）由两个蛋白质相互作用结构域组成，Toll/白细胞介素-1受体结构域（存在于MyD 88和Toll样受体中）和死亡结构域（存在于MyD 88和白细胞介素-1受体相关激酶中）。北方印迹实验和原位杂交研究表明，LPS处理后，LPS相互作用蛋白的水平保持不变，而MyD 88强烈上调。穿孔素样分子（M-r 74，171），巨噬细胞表达的蛋白质，被确定为该途径的执行分子。该基因在LPS处理后高度表达，特别是在动物的表面。重组蛋白具有生物活性，对革兰氏阴性菌有杀灭作用，对革兰氏阳性菌无活性。这些数据表明S. domuncula具有针对革兰氏阴性菌的先天免疫系统;配体LPS（病原体相关分子模式）被模式识别受体（LPS相互作用蛋白）识别，该模式识别受体与MyD 88相互作用。建立信号转导，其导致MyD 88以及作为执行蛋白的巨噬细胞表达蛋白的表达升高。
Sponges ( phylum Porifera) are the phylogenetically oldest metazoa; as filter feeders, they are abundantly exposed to marine microorganisms. Here we present data indicating that the demosponge Suberites domuncula is provided with a recognition system for Gram-negative bacteria. The lipopolysaccharide (LPS)-interacting protein was identified as a receptor on the sponge cell surface, which recognizes the bacterial endotoxin LPS. The cDNA was isolated, and the protein (M-r 49,937) was expressed. During binding to LPS, the protein dimerizes and interacts with MyD88, which was also identified and cloned. The sponge MyD88 (M-r 28,441) is composed of two protein interaction domains, a Toll/interleukin-1 receptor domain (found in MyD88 and in Toll-like receptors) and a death domain (present in MyD88 and interleukin-1 receptor-associated kinase). Northern blot experiments and in situ hybridization studies showed that after LPS treatment, the level of the LPS-interacting protein remains unchanged, whereas MyD88 is strongly up-regulated. A perforin-like molecule (M-r 74,171), the macrophage-expressed protein, was identified as an executing molecule of this pathway. This gene is highly expressed after LPS treatment, especially at the surfaces of the animals. The recombinant protein possesses biological activity and eliminates Gram-negative bacteria; it is inactive against Gram-positive bacteria. These data indicate that S. domuncula is provided with an innate immune system against Gramnegative bacteria; the ligand LPS (a pathogen-associated molecular pattern) is recognized by the pattern recognition receptor (LPS-interacting protein), which interacts with MyD88. A signal transduction is established, which results in an elevated expression of MyD88 as well as of the macrophage-expressed protein as an executing protein.