UCD School of Veterinary Medicine, University College Dublin, Dublin, 4, Ireland.
UCD School of Agriculture and Food Science, University College Dublin, Dublin, 4, Ireland.
Parasite Immunol. 2024 Apr;46(4):e13033. doi: 10.1111/pim.13033.
Canine demodicosis is a prevalent skin disease caused by overpopulation of a commensal species of Demodex mite, yet its precise cause remains unknown. Research suggests that T-cell exhaustion, increased immunosuppressive cytokines, induction of regulatory T cells and increased expression of immune checkpoint inhibitors may contribute to its pathogenesis. This study aimed to gain a deeper understanding of the molecular changes occurring in canine demodicosis using mass spectrometry and pathway enrichment analysis. The results indicate that endoplasmic reticulum stress promotes canine demodicosis through regulation of three linked signalling pathways: eIF2, mTOR, and eIF4 and p70S6K. These pathways are involved in the modulation of Toll-like receptors, most notably TLR2, and have been shown to play a role in the pathogenesis of skin diseases in both dogs and humans. Moreover, these pathways are also implicated in the promotion of immunosuppressive M2 phenotype macrophages. Immunohistochemical analysis, utilising common markers of dendritic cells and macrophages, verified the presence of M2 macrophages in canine demodicosis. The proteomic analysis also identified immunological disease, organismal injury and abnormalities and inflammatory response as the most significant underlying diseases and disorders associated with canine demodicosis. This study demonstrates that Demodex mites, through ER stress, unfolded protein response and M2 macrophages contribute to an immunosuppressive microenvironment, thereby assisting in their proliferation.
犬蠕形螨病是一种由共生的蠕形螨过度繁殖引起的常见皮肤病，但确切病因尚不清楚。研究表明，T 细胞耗竭、免疫抑制细胞因子增加、调节性 T 细胞的诱导和免疫检查点抑制剂的表达增加可能导致其发病机制。本研究旨在使用质谱和途径富集分析深入了解犬蠕形螨病发生的分子变化。结果表明，内质网应激通过调节三个相关信号通路：eIF2、mTOR 和 eIF4 和 p70S6K，促进犬蠕形螨病的发生。这些途径参与 Toll 样受体的调节，特别是 TLR2，并已被证明在犬和人类的皮肤病发病机制中发挥作用。此外，这些途径还与促进免疫抑制 M2 表型巨噬细胞有关。利用树突状细胞和巨噬细胞的常见标志物进行免疫组织化学分析，证实了犬蠕形螨病中存在 M2 巨噬细胞。蛋白质组学分析还确定了免疫性疾病、机体损伤和异常以及炎症反应是与犬蠕形螨病相关的最重要的潜在疾病和障碍。本研究表明，蠕形螨通过内质网应激、未折叠蛋白反应和 M2 巨噬细胞促进免疫抑制微环境，从而有助于其增殖。
