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猪 toll 样受体 2(TLR2)和 TLR4 的品种相关多态性及其与预防肺炎支原体和细菌 LPS 挑战的初步关系研究。

Breed-linked polymorphisms of porcine toll-like receptor 2 (TLR2) and TLR4 and the primary investigation on their relationship with prevention against Mycoplasma pneumoniae and bacterial LPS challenge.

机构信息

Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, People's Republic of China.

出版信息

Immunogenetics. 2013 Nov;65(11):829-34. doi: 10.1007/s00251-013-0727-4. Epub 2013 Aug 22.

DOI:10.1007/s00251-013-0727-4
PMID:23974322
Abstract

Toll-like receptors (TLRs) play a crucial role in innate immunity, serving as pattern-recognition receptors and the first barrier in host defense against microbial infections. Genetic variations of TLR2 and TLR4 are closely associated with a variety of infectious diseases, particularly lung diseases. In this study, we detected six and four single nucleotide polymorphisms (SNPs) in the coding sequences of porcine TLR2 and TLR4 genes, respectively. Only SNP 1027C>A of TLR4 was shown to be markedly biased in Western and Oriental pig populations. Hence, the susceptibility of pigs with different genotype at position 1027C>A to Mycoplasma hyopneumoniae (Mhp) infection was investigated, and changes to the expression of TLR2, TLR4, TNF-α and IL-1β were monitored. The results showed that there was no significant difference in susceptibility to Mhp infection between AA and CC individuals despite expression levels for all detected genes of the challenge groups being significantly higher than the corresponding control groups. Furthermore, porcine alveolar macrophages of different genotype were collected and stimulated by lipopolysaccharide. We found that the expression of TLR2, TLR4, TNF-α and IL-1β genes were enhanced to different levels by lipopolysaccharide stimulation. TLR2 and TLR4 gene expressions and their rates of increase of 1027CC pigs were significantly higher than for 1027AC pigs (P < 0.01), while TNF-α and IL-1β expressions were significantly lower than for 1027AC pigs (P < 0.01). We predict that allele C at position 1027 of the TLR4 gene contributes to the pig's immune response to gram-negative bacterial infections.

摘要

Toll 样受体(TLRs)在先天免疫中发挥着至关重要的作用,作为模式识别受体和宿主防御微生物感染的第一道防线。TLR2 和 TLR4 的遗传变异与多种传染病密切相关,尤其是肺部疾病。在本研究中,我们分别检测了猪 TLR2 和 TLR4 基因编码序列中的 6 个和 4 个单核苷酸多态性(SNPs)。仅 TLR4 的 SNP1027C>A 在西方和东方猪群中表现出明显的偏倚。因此,研究了不同 TLR41027C>A 基因型猪对支原体肺炎(Mhp)感染的易感性,并监测了 TLR2、TLR4、TNF-α 和 IL-1β 的表达变化。结果表明,尽管所有检测的挑战组基因的表达水平明显高于相应的对照组,但 AA 和 CC 个体对 Mhp 感染的易感性没有差异。此外,收集了不同基因型的猪肺泡巨噬细胞,并通过脂多糖刺激它们。我们发现,TLR2、TLR4、TNF-α 和 IL-1β 基因的表达在不同程度上被脂多糖刺激增强。TLR2 和 TLR4 基因的表达及其 1027CC 猪的增长率明显高于 1027AC 猪(P<0.01),而 TNF-α 和 IL-1β 的表达明显低于 1027AC 猪(P<0.01)。我们预测 TLR4 基因第 1027 位的等位基因 C 有助于猪对革兰氏阴性菌感染的免疫反应。

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