Vaz-Rodrigues Rita, de la Fuente José
SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.
Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma, USA.
FASEB J. 2025 May 15;39(9):e70602. doi: 10.1096/fj.202500687R.
The alpha-Gal syndrome (AGS) is an underdiagnosed tick-borne allergy characterized by both immediate and delayed IgE-mediated anaphylactic reactions to the galactose-alpha-1,3-galactose (alpha-Gal) epitope. Common manifestations include gastrointestinal, cutaneous, and respiratory symptoms appearing 2-6 h after the consumption of mammalian meat or derived products. Zebrafish (Danio rerio) are emerging as essential animal models in biomedical studies, due to their anatomical, genetic, and physiological similarities to humans, with significant applications in toxicology, behavioral research, oncology, and inflammation studies. The mechanisms associated with AGS are sustained by studies in the humanized α1,3GalT-KO C57BL/6 mouse (Mus musculus) and zebrafish animal models for the production of anti-alpha-Gal antibodies in response to tick saliva, the development of allergic reactions in animals sensitized with tick protein extracts following mammalian meat consumption, and the identification of immune mechanisms. The immune mechanisms characterized in both models are associated with a skewed type 2 immune response, triggering Toll-Like receptor (TLR) signaling pathways, IL-4 production, and humoral activity. These results support the use of both models rather than a single one for a more comprehensive characterization of AGS-associated immune mechanisms. In this study, we focused on the use of zebrafish as a model for biomedicine research in immunity, infectious, and allergic diseases, with a particular emphasis on the AGS and the identification of candidate therapeutic interventions. Based on insights from multiple studies, we concluded that zebrafish is a suitable model for studying the AGS, considering the addressed limitations and in combination with the α1,3GalT-KO mouse model.
α-半乳糖综合征（AGS）是一种诊断不足的蜱传播性过敏症，其特征为对半乳糖-α-1,3-半乳糖（α-Gal）表位产生即时和延迟的IgE介导的过敏反应。常见表现包括在食用哺乳动物肉类或衍生产品后2至6小时出现的胃肠道、皮肤和呼吸道症状。斑马鱼（Danio rerio）正成为生物医学研究中的重要动物模型，因为它们在解剖学、遗传学和生理学上与人类相似，在毒理学、行为研究、肿瘤学和炎症研究中有重要应用。与AGS相关的机制通过在人源化α1,3GalT-KO C57BL/6小鼠（小家鼠）和斑马鱼动物模型中的研究得以维持，这些研究涉及因蜱唾液产生抗α-Gal抗体、食用哺乳动物肉类后用蜱蛋白提取物致敏的动物发生过敏反应以及免疫机制的鉴定。在这两种模型中表征的免疫机制都与偏向性的2型免疫反应相关，触发Toll样受体（TLR）信号通路、IL-4产生和体液活性。这些结果支持使用这两种模型而非单一模型来更全面地表征与AGS相关的免疫机制。在本研究中，我们专注于将斑马鱼用作免疫、感染和过敏性疾病生物医学研究的模型，特别强调AGS以及候选治疗干预措施的鉴定。基于多项研究的见解，考虑到所解决的局限性并结合α1,3GalT-KO小鼠模型，我们得出结论，斑马鱼是研究AGS的合适模型。
