Creating a bovine C-type lectin receptor atlas and identification of their ligands

先天免疫系统是抵御病原体入侵的第一道防线。先天免疫系统的细胞，如巨噬细胞和树突状细胞表达多种结合糖（聚糖）靶标的受体。这些受体被称为凝集素，具有双重功能：在非感染性条件下，它们通过增强巨噬细胞/树突状细胞与T细胞的相互作用来支持免疫系统的正常功能。在感染条件下，它们在感染的情况下帮助识别表达特定聚糖基序的病原体。通过这些受体将宿主细胞与病原体区分开来，源于它们结合病原体特异性表面糖的能力。最近，研究人员探索了利用多糖结构作为疫苗佐剂/疫苗递送系统，通过糖结合受体靶向特异性先天免疫细胞亚群的想法。使用这种方法在小鼠中诱导了强大的体液和细胞免疫反应。因此，除了更详细地了解农场动物的先天免疫细胞- T细胞相互作用外，所提出的工作将为利用聚糖本身的佐剂样特性提供基础，这些特性是由于它们能够激活抗原呈递细胞上表达的炎症和吞噬受体。我们的初步数据表明，在不同哺乳动物物种中表达的聚糖受体及其识别的配体之间存在实质性差异。这一观察结果对农场动物（特别是本文所研究的反刍动物）的疫苗设计具有重要意义，因为这意味着在人类和/或小鼠系统中设计和测试的疫苗佐剂可能不适用于其他哺乳动物物种，最近分枝杆菌疫苗在适当宿主中的失败支持了这一事实。因此，鉴定牛基因组中的聚糖（凝集素）受体并了解其功能可能为了解宿主与病原体相互作用的第一步提供新的途径。由于减少抗生素依赖的关键途径，因此减少抗菌素耐药性是改善当前的疫苗策略，所获得的知识也可能为开发更具宿主特异性的佐剂/疫苗递送系统提供基础。

The innate immune system is the first line of defence against invading pathogens. Cells of the innate immune system, such as macrophages and dendritic cells express a variety of receptors that bind to sugar (glycan) targets. These receptors, known as lectins, perform a dual function: under non-infectious conditions, they support the normal function of the immune system through enhancing the interaction of macrophages/dendritic cells with T cells. Under infectious conditions, they aide the recognition of pathogens that express specific glycan motifs in case of an infection. Distinguishing host cells from pathogens by these receptors derives from their ability to bind pathogen-specific surface sugars.Recently, the idea of using glycan structures as vaccine adjuvants/vaccine delivery systems to target specific innate immune cell subsets through the sugar-binding receptors has been explored. Using this approach robust humoral and cellular immune responses have been induced in mice. Thus, in addition to providing an understanding of innate immune cell - T cell interaction in farm animals in more detail, the proposed work will provide a basis for exploiting adjuvant-like properties of glycans themselves resulting from their ability to activate both inflammatory and phagocytic receptors expressed on antigen-presenting cells. Our preliminary data demonstrate that there are substantial differences between the glycan-receptors expressed in different mammalian species, and the ligands that they recognise. This observation has important implications for vaccine design for farm animals, specifically ruminants as studied here, as it means that vaccine adjuvants designed and tested in the human and/or murine system may not work in other mammalian species, a fact supported by the recent failure of mycobacterial vaccines in the appropriate host. Thus, identifying the glycan (lectin) receptors in the bovine genome and understanding their function may provide new avenues to understand the first steps in host pathogen interaction. As the key way of reducing antibiotic dependence, and thus the reduction of AMR is to improve current vaccine strategies, the gained knowledge may also provide the basis for the development of more host-specific adjuvant/vaccine-delivery systems.