Maldonado-Ruiz L Paulina, Boorgula Gunavanthi D, Kim Donghun, Fleming Sherry D, Park Yoonseong
Department of Entomology, Kansas State University, Manhattan, KS, United States.
Department of Entomology, Kyungpook National University, Daegu, South Korea.
Front Immunol. 2022 Mar 4;13:844262. doi: 10.3389/fimmu.2022.844262. eCollection 2022.
Recent studies have provided strong evidence indicating that lone star tick bites are a cause of AGS (alpha-gal syndrome, also known as red meat allergy RMA) in humans. AGS is characterized by an increase in IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan found in mammalian tissue, except in Old World monkeys and humans. The main causative factor of AGS, the lone star tick (), is broadly distributed throughout the east and midwest of the United States and is a vector of a wide range of human and animal pathogens. Our earlier glycomics study of the salivary glands of partially fed male and female ticks revealed relatively high levels of aGal epitopes. In this study, we found that partially fed males of on bovine blood, which engage in multiple intrastadial feedings, carry a large amount of aGal in the salivary glands. In our current work, we aimed to test whether ticks mediate the transmission of the aGal sensitizer acquired from nonhuman blood to humans in the intrastadial host switch (referred to as the "transmission" hypothesis). To test this hypothesis, we used an alpha-galactosyltransferase knockout mutant mouse (aGT-KO) model system infested with ticks that were unfed or partially fed on bovine blood. Based on the levels of total IgE and specific IgG and IgE antibodies against aGal after tick feedings, aGT-KO mice significantly responded to tick feeding and injection of aGal (Galα1-3Galβ1-4GlcNAc) conjugated to human serum albumin or mouse serum albumin (aGal-HSA or aGal-MSA) by increasing total IgE and aGal-specific IgE levels compared to those in C57BL/6 control mice. All of the treatments of aGT-KO mice involving the feeding of partially fed and unfed ticks functioned as sensitizers that increased the levels of specific IgE against aGal, with large individual variations. The data in this study do not support the "transmission" component of AGS, although they confirmed that aGT-KO mice can be used as a model for RMA studies.
最近的研究提供了强有力的证据，表明孤星蜱叮咬是人类患上 AGS（α-半乳糖综合征，也称为红肉过敏症，RMA）的一个原因。AGS 的特征是针对半乳糖-α-1,3-半乳糖（aGal）的 IgE 抗体产生增加，aGal 是一种在哺乳动物组织中常见的聚糖，但在旧世界猴和人类中除外。AGS 的主要致病因素——孤星蜱，广泛分布于美国东部和中西部，是多种人类和动物病原体的传播媒介。我们早期对部分饱血的雄性和雌性蜱唾液腺的糖组学研究发现，aGal 表位水平相对较高。在本研究中，我们发现以牛血为食、经历多次蜕变态进食的部分饱血雄性孤星蜱，其唾液腺中携带大量 aGal。在我们目前的工作中，我们旨在测试蜱是否介导了在蜕变态宿主转换过程中从非人类血液获取的 aGal 致敏原向人类的传播（称为“传播”假说）。为了验证这一假说，我们使用了一种α-半乳糖基转移酶基因敲除突变小鼠（aGT-KO）模型系统，用未进食或部分饱血于牛血的蜱进行感染。根据蜱进食后针对 aGal 的总 IgE 以及特异性 IgG 和 IgE 抗体水平，与 C57BL/6 对照小鼠相比，aGT-KO 小鼠通过增加总 IgE 和 aGal 特异性 IgE 水平，对蜱进食以及注射与人血清白蛋白或小鼠血清白蛋白偶联的 aGal（Galα1-3Galβ1-4GlcNAc）（aGal-HSA 或 aGal-MSA）有显著反应。涉及喂食部分饱血和未进食蜱的所有 aGT-KO 小鼠处理都起到了致敏剂的作用，增加了针对 aGal 的特异性 IgE 水平，个体差异较大。本研究中的数据不支持 AGS 的“传播”成分，尽管它们证实了 aGT-KO 小鼠可作为 RMA 研究的模型。
