BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, BC, Canada; Department of Surgery, University of British Columbia, BC, Canada.
Trends Immunol. 2019 Aug;40(8):762-780. doi: 10.1016/j.it.2019.06.005. Epub 2019 Jul 15.
Amyloid formation contributes to the development of progressive metabolic and neurodegenerative diseases, while also serving functional roles in host defense. Emerging evidence suggests that as amyloidogenic peptides populate distinct aggregation states, they interact with different combinations of pattern recognition receptors (PRRs) to direct the phenotype and function of tissue-resident and infiltrating innate immune cells. We review recent evidence of innate immunomodulation by distinct forms of amyloidogenic peptides produced by mammals (humans, non-human primates), bacteria, and fungi, as well as the corresponding cell-surface and intracellular PRRs in these interactions, in human and mouse models. Our emerging understanding of peptide aggregate-innate immune cell interactions, and the factors regulating the balance between amyloid function and pathogenicity, might aid the development of anti-amyloid and immunomodulating therapies.
淀粉样蛋白的形成有助于进行性代谢和神经退行性疾病的发展，同时在宿主防御中也具有功能作用。新出现的证据表明，随着淀粉样蛋白肽进入不同的聚集状态，它们与不同组合的模式识别受体（PRRs）相互作用，以指导组织驻留和浸润性固有免疫细胞的表型和功能。我们回顾了哺乳动物（人类、非人类灵长类动物）、细菌和真菌产生的不同形式的淀粉样蛋白肽，以及在人类和小鼠模型中这些相互作用中的相应细胞表面和细胞内 PRRs 对固有免疫的调节作用的最新证据。我们对肽聚集-固有免疫细胞相互作用的理解不断加深，以及调节淀粉样蛋白功能和致病性之间平衡的因素，可能有助于开发抗淀粉样蛋白和免疫调节疗法。
