Heilmann Romy M, Allenspach Karin
Department of Small Animal Medicine, College of Veterinary Medicine, University of Leipzig, Leipzig, Saxony, Germany (Heilmann).
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA (Allenspach).
J Vet Diagn Invest. 2017 Nov;29(6):781-787. doi: 10.1177/1040638717728545. Epub 2017 Sep 14.
Pattern-recognition receptors (PRRs) are expressed by innate immune cells and recognize pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular pattern (DAMP) molecules. With a large potential for synergism or convergence between their signaling pathways, PRRs orchestrate a complex interplay of cellular mediators and transcription factors, and thus play a central role in homeostasis and host defense. Aberrant activation of PRR signaling, mutations of the receptors and/or their downstream signaling molecules, and/or DAMP/PAMP complex-mediated receptor signaling can potentially lead to chronic auto-inflammatory diseases or development of cancer. PRR signaling pathways appear to also present an interesting new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets. Evidence for a dysregulation of the PRR toll-like receptor (TLR)2, TLR4, TLR5, and TLR9, nucleotide-binding oligomerization domain-containing protein (NOD)2, and the receptor of advanced glycation end products (RAGE) exists in dogs with chronic enteropathies. We describe the TLR, NOD2, and RAGE signaling pathways and evaluate the current veterinary literature-in comparison to human medicine-to determine the role of TLRs, NOD2, and RAGE in canine chronic enteropathies.
模式识别受体（PRRs）由固有免疫细胞表达，可识别病原体相关分子模式（PAMPs）以及内源性损伤相关分子模式（DAMP）分子。由于其信号通路之间具有巨大的协同或汇聚潜力，PRRs协调细胞介质和转录因子的复杂相互作用，因此在体内平衡和宿主防御中发挥核心作用。PRR信号的异常激活、受体和/或其下游信号分子的突变，和/或DAMP/PAMP复合物介导的受体信号传导可能会导致慢性自身炎症性疾病或癌症的发生。PRR信号通路似乎也为调节炎症反应提供了一个有趣的新途径，并可作为潜在的新型治疗靶点。患有慢性肠病的犬只存在PRR Toll样受体（TLR）2、TLR4、TLR5和TLR9、含核苷酸结合寡聚化结构域蛋白（NOD）2以及晚期糖基化终产物受体（RAGE）失调的证据。我们描述了TLR、NOD2和RAGE信号通路，并与人类医学相比评估当前的兽医文献，以确定TLR、NOD2和RAGE在犬慢性肠病中的作用。
