Gram-negative bacteria-binding protein, a pattern recognition receptor for lipopolysaccharide and β-1,3-glucan that mediates the signaling for the induction of innate immune genes in drosophila melanogaster cells
Gram-negative bacteria-binding protein, a pattern recognition receptor for lipopolysaccharide and β-1,3-glucan that mediates the signaling for the induction of innate immune genes in drosophila melanogaster cells
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DOI：
10.1074/jbc.m003934200
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发表时间：
2000-10-20
影响因子：
4.8
通讯作者：
Lee, WJ
中科院分区：
文献类型：
--
作者：
Kim, YS;Ryu, JH;Lee, WJ
模式识别受体是识别常见微生物组分的非克隆免疫蛋白，对于非自我识别和随后诱导Rel/NF-κ B控制的先天免疫基因至关重要。然而，这种受体的分子身份仍然是模糊的。在此，我们提供的数据显示果蝇具有至少三个编码革兰氏阴性细菌结合蛋白（DGNBP）家族成员的cDNA，其中一个DGNBP-1已被表征。Western印迹、流式细胞术和激光共聚焦显微镜分析表明，DGNSP-1在培养基上清液和果蝇免疫活性细胞中以可溶性和糖基磷脂酰肌醇锚定膜形式存在，分别DGNBP-1对微生物免疫激发物如脂多糖（LPS）和β-1，3-葡聚糖具有高亲和力，而对肽聚糖、β-1，4-葡聚糖或几丁质没有检测到结合亲和力。重要的是，DGNBP-1在果蝇免疫活性细胞中的过表达增强LPS和β-1，5-葡聚糖诱导的先天免疫基因，这些结果表明，DGNBP-1作为来自革兰氏阴性菌的LPS和β-1，3-葡聚糖在果蝇天然免疫系统中的非自我识别和随后的免疫信号传递中起重要作用，从而诱导抗菌肽基因。
Pattern recognition receptors, non-clonal immune proteins recognizing common microbial components, are critical for non-self recognition and the subsequent induction of Rel/NF-kappaB-controlled innate immune genes. However, the molecular identities of such receptors are still obscure. Here, we present data showing that Drosophila possesses at least three cDNAs encoding members of the Gram-negative bacteria-binding protein (DGNBP) family, one of which, DGNBP-1, has been characterized, Western blot, flow cytometric, and confocal laser microscopic analyses demonstrate that DGNSP-1 exists in both a soluble and a glycosylphosphatidylinositol-anchored membrane form in culture medium supernatant and on Drosophila immunocompetent cells, respectively. DGNBP-1 has a high affinity to microbial immune elicitors such as lipopolysaccharide (LPS) and beta -1,3-glucan whereas no binding affinity is detected with peptidoglycan, beta -1,4-glucan, or chitin, Importantly, the overexpression of DGNBP-1 in Drosophila immunocompetent cells enhances LPS- and beta -1,5-glucan-induced innate immune gene (NF-kappaB-dependent antimicrobial peptide gene) expression, which can be specifically blocked by pretreatment with anti-DGNBP-1 antibody, These results suggest that DGNBP-1 functions as a pattern recognition receptor for LPS from Gram-negative bacteria and beta -1,3-glucan from fungi and plays an important role in non-self recognition and the subsequent immune signal transmission for the induction of antimicrobial peptide genes in the Drosophila innate immune system.