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Allelic Variation in TLR4 Is Linked to Susceptibility to Salmonella enterica Serovar Typhimurium Infection in Chickens

机译:TLR4的等位基因变异与鸡沙门氏菌血清型鼠伤寒感染的易感性有关

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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-interleukin-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.
机译:Toll样受体4(TLR4)是一组进化上保守的模式识别受体的一部分,参与了对各种病原体的免疫系统的激活以及对感染的先天防御。我们在这里描述哺乳动物 TLR4 禽直系同源物的克隆和鉴定。鸡 TLR4 编码一个843个氨基酸的蛋白质,其中包含一个富含亮氨酸的重复细胞外结构域,一个典型的I型跨膜蛋白短跨膜结构域以及一个具有所有特征的Toll-interleukin-1R信号结构域。 TLR蛋白。鸡TLR4蛋白与人TLR4的同源性为46%(相似性为64%),与其他TLR家族成员的同源性为41%。 Northern印迹分析表明, TLR4 在所有测试组织中的表达水平大致相同,包括脑,胸腺,肾脏,肠,肌肉,肝,肺,法氏囊,心脏和脾脏。探针仅检测到约一个转录本。除 TLR4 mRNA大小为肌肉的肌肉外,所有组织的长度均为4.4 kb。 9.6 KB。我们已经将 TLR4 映射到微染色体E41W17,该区域包含腱糖蛋白C的基因,并且已知在鸡和哺乳动物基因组之间保存良好。先前已证明鸡基因组的该区域具有沙门氏菌易感性基因座。通过连锁分析,表明 TLR4 与鸡对沙门氏菌血清型鼠伤寒的抗性相关(似然比检验为10.2, P > = 0.00138),表明TLR4在鸡对沙门氏菌感染的宿主反应中发挥了作用。

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