LvCD14L Acts as a Novel Pattern Recognition Receptor and a Regulator of the Toll Signaling Pathway in Shrimp.

LvCD14L Acts as a Novel Pattern Recognition Receptor and a Regulator of the Toll Signaling Pathway in Shrimp.
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DOI:
10.3390/ijms24097770
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发表时间:
2023-04-24
影响因子:
5.6
通讯作者:
Li, Fuhua
Li, Fuhua
中科院分区:
生物学2区
文献类型:
--
作者:
Lv, Xinjia;Li, Shihao;Yu, Yang;Jin, Songjun;Zhang, Xiaojun;Li, Fuhua

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富含亮氨酸重复序列(Leucine-rich repeat,LRR)是一类在免疫受体如Toll和NOD样受体(NLR)中具有重要识别功能的结构基序。免疫相关的LRR蛋白可分为两类,含LRR的蛋白和仅含LRR的蛋白。后者含有LRR基序,而它们没有其他功能结构域。然而,LRR蛋白在无脊椎动物中的功能机制仍不清楚。在这里,我们确定了一个基因编码的分泌型LRR的唯一蛋白质,具有与脊椎动物的CD 14的相似性,并被命名为LvCD 14 L,从太平洋白对虾凡纳滨对虾。其在对虾血细胞中的转录产物对副溶血弧菌的感染有明显的反应。用dsRNA敲除LvCD 14 L导致副溶血弧菌感染后虾肝胰腺中活菌的显著增加。进一步的功能研究表明,LvCD 14 L可以与微生物的PAMPs结合,与LvToll 1和LvToll 2相互作用,调节LvDorsal和LvALF 2在血细胞中的表达。这些结果表明,LvCD 14 L作为模式识别受体发挥功能,并通过与LvTolls相互作用激活NF-κB通路。本研究揭示了对虾LvCD 14 L-Tolls-NF-κB信号通路类似于对虾的CD 14/TLR 4/NF-κB信号通路,丰富了无脊椎动物病原体感染过程中分泌型LRR免疫受体的功能机制。
Leucine-rich repeat (LRR) is a structural motif has important recognition function in immune receptors, such as Tolls and NOD-like receptors (NLRs). The immune-related LRR proteins can be divided into two categories, LRR-containing proteins and LRR-only proteins. The latter contain LRR motifs while they are without other functional domains. However, the functional mechanisms of the LRR-only proteins were still unclear in invertebrates. Here, we identified a gene encoding a secretory LRR-only protein, which possessed similarity with vertebrate CD14 and was designated as LvCD14L, from the Pacific whiteleg shrimp Litopenaeus vannamei. Its transcripts in shrimp hemocytes were apparently responsive to the infection of Vibrio parahaemolyticus. Knockdown of LvCD14L with dsRNA resulted in significant increase of the viable bacteria in the hepatopancreas of shrimp upon V. parahaemolyticus infection. Further functional studies revealed that LvCD14L could bind to microorganisms’ PAMPs, showed interaction with LvToll1 and LvToll2, and regulated the expression of LvDorsal and LvALF2 in hemocytes. These results suggest that LvCD14L functions as a pattern recognition receptor and activates the NF-κB pathway through interaction with LvTolls. The present study reveals a shrimp LvCD14L-Tolls-NF-κB signaling pathway like the CD14/TLR4/NF-κB signaling pathway in mammalians, which enriches the functional mechanism of secretory LRR-only immune receptors during pathogens infection in invertebrates.
DOI: 10.1038/nature02740
发表时间: 2004-07-08
期刊: NATURE
影响因子: 64.8
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