Toll9 from Bombyx mori functions as a pattern recognition receptor that shares features with Toll-like receptor 4 from mammals

文献类型: 外文期刊

第一作者: Zhang, Ruonan

作者: Zhang, Ruonan;Li, Xiaofeng;Wang, Yuan;Song, Yuhang;Ren, Feifei;Yi, Huiyu;Deng, Xiaojuan;Zhong, Yangjin;Cao, Yang;Yang, Wanying;Zhang, Ruonan;Zhang, Jie;Li, Yanjun;Yu, Xiao-Qiang;Cao, Yang;Cao, Yang;Strand, Michael R.

作者机构:

关键词: immunity; lipopolysaccharide; ML proteins; MD-2; Toll

期刊名称:PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA ( 影响因子:9.412; 五年影响因子:10.62 )

ISSN: 0027-8424

年卷期: 2021 年 118 卷 19 期

页码:

收录情况: SCI

摘要: Toll/Toll-like receptors (TLRs) are key regulators of the innate immune system in both invertebrates and vertebrates. However, while mammalian TLRs directly recognize pathogen-associated molecular patterns, the insect Toll pathway is thought to be primarily activated by binding Spatzle cytokines that are processed from inactive precursors in response to microbial infection. Phylogenetic and structural data generated in this study supported earlier results showing that Toll9 members differ from other insect Tolls by clustering with the mammalian TLR4 group, which recognizes lipopolysaccharide (LPS) through interaction with myeloid differentiation-2 (MD-2)-like proteins. Functional experiments showed that BmToll9 from the silkmoth Bombyx mori also recognized LPS through interaction with two MD-2-like proteins, previously named BmEsr16 and BmPP, that we refer to in this study as BmMD-2A and BmMD-2B, respectively. A chimeric BmToll9-TLR4 receptor consisting of the BmToll9 ectodomain and mouse TLR4 transmembrane and Toll/ interleukin-1 (TIR) domains also activated LPS-induced release of inflammatory factors in murine cells but only in the presence of BmMD-2A or BmMD-2B. Overall, our results indicate that BmToll9 is a pattern recognition receptor for LPS that shares conserved features with the mammalian TLR4-MD-2-LPS pathway.

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