Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide.
Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide.
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DOI：
10.3389/fimmu.2018.00304
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发表时间：
2018
影响因子：
7.3
通讯作者：
Harms MJ
中科院分区：
文献类型：
--
作者：
Loes AN;Bridgham JT;Harms MJ
Toll样受体4（TLR 4）诱导炎症反应的病原体和宿主来源的分子。脂多糖（LPS）的识别TLR 4已被证明发生在整个胎盘，但内源性信号转导通过TLR 4尚未被证实以外的胎盘哺乳动物。为了确定内源性危险信号是否也在胎盘动物中共享，我们研究了钙颗粒蛋白（S100 A8，S100 A9和S100 A12）激活TLR 4的进化，这是一种在胎盘哺乳动物中有效激活TLR 4的宿主分子。我们进行了系统发育和同线分析，发现MRP-126-一个基因在鸟类和爬行动物-可能是直系的哺乳动物calgranulins。然后，我们使用离体TLR 4激活试验来确定钙颗粒蛋白促炎活性并不特异于胎盘哺乳动物，但代表性的有袋动物和蜥脚类动物也表现出这种活性。对于所有研究的物种，这种活性强烈依赖于辅因子CD 14和MD-2，这表明在所有物种中存在保守的激活模式。calgranulins、TLR 4、CD 14和MD-2之间的同源互补实验揭示了广泛的谱系特异性共进化和组分之间的多途径相互作用，这些组分是calgranulins和LPS激活NF-κB信号传导所必需的。我们的工作表明，TLR 4的钙颗粒蛋白激活至少在约3.2亿年前进化，并在灵长类先天免疫系统中保守。
Toll-like receptor 4 (TLR4) induces inflammation in response to both pathogen- and host-derived molecules. Lipopolysaccharide (LPS) recognition by TLR4 has been shown to occur across the amniotes, but endogenous signaling through TLR4 has not been validated outside of placental mammals. To determine whether endogenous danger signaling is also shared across amniotes, we studied the evolution of TLR4-activation by the calgranulin proteins (S100A8, S100A9, and S100A12), a clade of host molecules that potently activate TLR4 in placental mammals. We performed phylogenetic and syntenic analysis and found MRP-126—a gene in birds and reptiles—is likely orthologous to the mammalian calgranulins. We then used an ex vivo TLR4 activation assay to establish that calgranulin pro-inflammatory activity is not specific to placental mammals, but is also exhibited by representative marsupial and sauropsid species. This activity is strongly dependent on the cofactors CD14 and MD-2 for all species studied, suggesting a conserved mode of activation across the amniotes. Ortholog complementation experiments between the calgranulins, TLR4, CD14, and MD-2 revealed extensive lineage specific-coevolution and multi-way interactions between components that are necessary for the activation of NF-κB signaling by calgranulins and LPS. Our work demonstrates that calgranulin activation of TLR4 evolved at least ~320 million years ago and has been conserved in the amniote innate immune system.
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影响因子：
3.7
作者：
Björk P;Källberg E;Wellmar U;Riva M;Olsson A;He Z;Törngren M;Liberg D;Ivars F;Leanderson T
通讯作者：
Leanderson T
影响因子：
7.3
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Foell, D.;Wittkowski, H.;Clancy, R.
通讯作者：
Clancy, R.
影响因子：
4.1
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通讯作者：
Jerala, Roman
影响因子：
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Chen B;Miller AL;Rebelatto M;Brewah Y;Rowe DC;Clarke L;Czapiga M;Rosenthal K;Imamichi T;Chen Y;Chang CS;Chowdhury PS;Naiman B;Wang Y;Yang D;Humbles AA;Herbst R;Sims GP
通讯作者：
Sims GP
影响因子：
6.5
作者：
Anisimova, Maria;Gascuel, Olivier
通讯作者：
Gascuel, Olivier