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对鸡Toll样受体4和21的配体进行体内给药可诱导脾脏中免疫系统基因的表达。

In vivo administration of ligands for chicken toll-like receptors 4 and 21 induces the expression of immune system genes in the spleen.

作者信息

St Paul Michael, Mallick Amirul I, Haq Kamran, Orouji Shahriar, Abdul-Careem Mohamed Faizal, Sharif Shayan

机构信息

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

出版信息

Vet Immunol Immunopathol. 2011 Dec 15;144(3-4):228-37. doi: 10.1016/j.vetimm.2011.09.004. Epub 2011 Sep 29.

Abstract

Toll-like receptors (TLRs) are a group of conserved proteins that play an important role in pathogen recognition in addition to the initiation and regulation of innate and adaptive immune responses. To date, several TLRs have been identified in chickens, each recognizing different ligands. TLR stimulation in chickens has been shown to play a role in host-responses to pathogens. However, the mechanisms through which TLRs modulate the chicken immune system have not been well examined. The present study was conducted to characterize the kinetics of responses to TLR4 and TLR21 stimulation in chickens following intramuscular injections of their corresponding ligands, lipopolysaccharide (LPS) and CpG oligodeoxynucleotides (ODNs), respectively. To this end, relative expression of cytokine genes in the spleen was determined at 2, 6, 12 and 24 h after injection of TLR ligands. The results indicated that LPS strongly induced the up-regulation of some immune system genes early on in the response to treatment, including interferon (IFN)-γ, interleukin (IL)-10, and IL-1β. Furthermore, treatment with CpG ODN promoted the up-regulation of major histocompatibility complex (MHC)-II, IFN-γ and IL-10. The response to CpG ODN appeared to be somewhat delayed compared to the response to LPS. Moreover, we found a significant increase in IFN-α gene expression in response to LPS but not CpG ODNs. Future studies may be aimed to further characterize the molecular mechanisms of TLR activation in chickens or to exploit TLR agonists as vaccine adjuvants.

摘要

Toll样受体(TLRs)是一组保守蛋白,除了在先天性和适应性免疫反应的启动和调节中发挥作用外,在病原体识别中也起着重要作用。迄今为止,已在鸡中鉴定出几种TLR,每种识别不同的配体。鸡中的TLR刺激已被证明在宿主对病原体的反应中起作用。然而,TLR调节鸡免疫系统的机制尚未得到充分研究。本研究旨在分别通过肌肉注射其相应配体脂多糖(LPS)和CpG寡脱氧核苷酸(ODN)来表征鸡对TLR4和TLR21刺激的反应动力学。为此,在注射TLR配体后2、6、12和24小时测定脾脏中细胞因子基因的相对表达。结果表明,LPS在对治疗的反应早期强烈诱导了一些免疫系统基因的上调,包括干扰素(IFN)-γ、白细胞介素(IL)-10和IL-1β。此外,用CpG ODN处理促进了主要组织相容性复合体(MHC)-II、IFN-γ和IL-10的上调。与对LPS的反应相比,对CpG ODN的反应似乎有所延迟。此外,我们发现对LPS反应时IFN-α基因表达显著增加,但对CpG ODNs无此现象。未来的研究可能旨在进一步表征鸡中TLR激活的分子机制,或开发TLR激动剂作为疫苗佐剂。

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