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

先天免疫系统是抵御入侵病原体的第一道防线。天然免疫系统的细胞，如巨噬细胞和树突状细胞，表达各种与糖(多糖)靶标结合的受体。这些被称为凝集素的受体具有双重功能：在非感染条件下，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，它们有助于识别在感染情况下表达特定糖链基序的病原体。通过这些受体区分宿主细胞和病原体源于它们结合病原体特异性表面糖的能力。最近，人们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定的天然免疫细胞亚群的想法。使用这种方法，已经在小鼠身上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与T细胞的相互作用外，这项拟议的工作还将为利用多糖本身的佐剂样特性提供基础，这些特性是由于多糖本身具有激活抗原呈递细胞上表达的炎症和吞噬细胞受体的能力而产生的。我们的初步数据表明，在不同的哺乳动物物种中表达的糖链受体和它们识别的配体之间存在着实质性的差异。这一观察结果对农场动物，特别是这里研究的反刍动物的疫苗设计具有重要意义，因为它意味着在人类和/或小鼠系统中设计和测试的疫苗佐剂可能在其他哺乳动物物种中不起作用，这一事实得到了分枝杆菌疫苗在适当宿主中失败的事实的支持。因此，鉴定牛基因组中的糖链(凝集素)受体并了解它们的功能可能会为理解宿主病原体相互作用的第一步提供新的途径。作为减少抗生素依赖的关键途径，因此减少AMR是改进现有疫苗策略的关键，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.