Allelic variation in TLR4 is linked to susceptibility to Salmonella enterica serovar typhimurium infection in chickens
Allelic variation in TLR4 is linked to susceptibility to Salmonella enterica serovar typhimurium infection in chickens
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DOI：
10.1128/iai.71.3.1116-1124.2003
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发表时间：
2003-03-01
影响因子：
3.1
通讯作者：
Malo, D
中科院分区：
文献类型：
--
作者：
Leveque, G;Forgetta, V;Malo, D
Toll样受体4（TLR 4）是一组进化上保守的模式识别受体的一部分，其参与响应于各种病原体的免疫系统的激活和针对感染的先天防御。我们在这里描述的克隆和鉴定的鸟类直系同源的哺乳动物TLR 4。鸡TLR 4编码一个843个氨基酸的蛋白质，包含一个富含亮氨酸的重复细胞外结构域，一个典型的I型跨膜蛋白的短跨膜结构域，和一个所有TLR蛋白的特征性Toll-白细胞介素-1R信号传导结构域。鸡TLR 4蛋白与人TLR 4的同源性为46%（64%相似性），与其他TLR家族成员的同源性为41%。北方印迹分析显示，TLR 4在所有测试的组织中以大致相同的水平表达，包括脑、胸腺、肾、肠、肌肉、肝、肺、腔上囊、心脏和脾。该探针仅检测到ca的一个转录本。4.4除肌肉外，其它组织中TLR 4 mRNA的大小约为1.2kb。9.6 KB.我们已经将TLR 4定位到微染色体E41 W17的一个区域，该区域包含腱生蛋白C基因，并且已知在鸡和哺乳动物基因组之间是非常保守的。鸡基因组的这一区域以前被证明含有沙门氏菌易感性位点。通过使用连锁分析，TLR 4被证明与鸡对沙门氏菌鼠伤寒血清型感染的抗性有关（似然比检验为10.2，P = 0.00138），表明TLR 4在鸡对沙门氏菌感染的宿主反应中起作用。
Toll-like receptor 4 (TLR4) is part of a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens and in the innate defense against infection. We describe here the cloning and characterization of the avian orthologue of mammalian TLR4. Chicken TLR4 encodes a 843-amino-acid protein that contains a leucine-rich repeat extracellular domain, a short transmembrane domain typical of type I transmembrane proteins, and a Toll-interieukin-1R signaling domain characteristic of all TLR proteins. The chicken TLR4 protein shows 46% identity (64% similarity) to human TLR4 and 41% similarity to other TLR family members. Northern blot analysis reveals that TLR4 is expressed at approximately the same level in all tissues tested, including brain, thymus, kidney, intestine, muscle, liver, lung, bursa of Fabricius, heart, and spleen. The probe detected only one transcript of ca. 4.4 kb in length for all tissues except muscle where the size of TLR4 mRNA was ca. 9.6 kb. We have mapped TLR4 to microchromosome E41W17 in a region harboring the gene for tenascin C and known to be well conserved between the chicken and mammalian genomes. This region of the chicken genome was shown previously to harbor a Salmonella susceptibility locus. By using linkage analysis, TLR4 was shown to be linked to resistance to infection with Salmonella enterica serovar Typhimurium in chickens (likelihood ratio test of 10.2, P = 0.00138), suggesting a role of TLR4 in the host response of chickens to Salmonella infection.