Induction of a novel chicken toll-like receptor following Salmonella enterica serovar Typhimurium infection
Induction of a novel chicken toll-like receptor following Salmonella enterica serovar Typhimurium infection
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DOI：
10.1128/iai.74.3.1692-1698.2006
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发表时间：
2006-03-01
影响因子：
3.1
通讯作者：
O'Farrelly, C
中科院分区：
文献类型：
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作者：
Higgs, R;Cormican, P;O'Farrelly, C
Toll样受体（TLR）是一类高度保守的分子，通过识别微生物表达的结构基序来启动针对病原体的先天性免疫应答。我们已经确定了一种新的TLR，TLR15，鸡基因组的生物信息学分析，这是不同于任何已知的脊椎动物TLR，因此似乎是鸟类特异性。TLR15的基因被测序并发现在3号染色体上，它具有原型TIR和跨膜结构域以及细胞外富含亮氨酸区域的独特排列。TLR15的mRNA在健康鸡的脾脏、法氏囊和骨髓中检测到，表明这种新型受体在组成型宿主防御中的作用。在体内肠道沙门氏菌血清型鼠伤寒感染后，定量实时PCR显示感染鸡盲肠中TLR15的显著上调。有趣的是，也观察到感染后类似的TLR2表达诱导。体外研究表明，热灭活S.鼠伤寒沙门氏菌总的来说，这些结果表明TLR在鸟类防御细菌感染中的作用。我们推测TLR15可能代表一种禽类特异性TLR，该TLR在鸡中保留并在其他类群中丢失或在鸡中获得。
Toll-like receptors (TLRs) are a group of highly conserved molecules that initiate the innate immune response to pathogens by recognizing structural motifs expressed by microbes. We have identified a novel TLR, TLR15, by bioinformatic analysis of the chicken genome, which is distinct from any known vertebrate TLR and thus appears to be avian specific. The gene for TLR15 was sequenced and is found on chromosome 3, and it has archetypal TIR and transmembrane domains and a distinctive arrangement of extracellular leucine-rich regions. mRNA for TLR15 was detected in the spleen, bursa, and bone marrow of healthy chickens, suggesting a role for this novel receptor in constitutive host defense. Following in vivo Salmonella enterica serovar Typhimurium infection, quantitative real-time PCR demonstrated significant upregulation of TLR15 in the cecum of infected chickens. Interestingly, similar induction of TLR2 expression following infection was also observed. In vitro studies revealed TLR15 upregulation in chicken embryonic fibroblasts stimulated with heat-killed S. enterica serovar Typhimurium. Collectively, these results suggest a role for the TLR in avian defense against bacterial infection. We hypothesize that TLR15 may represent an avian-specific TLR that has been either retained in chicken and lost in other taxa or gained in the chicken.