Creating a bovine C-type lectin receptor atlas and identification of their ligands
牛C型凝集素受体图谱的创建及其配体的鉴定
基本信息
- 批准号:BB/P008461/1
- 负责人:
- 金额:$ 58.02万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
先天免疫系统是抵御入侵病原体的第一道防线。先天免疫系统的细胞,如巨噬细胞和树突细胞,表达多种与糖(聚糖)靶结合的受体。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,它们有助于识别在感染情况下表达特异性聚糖基序的病原体。通过这些受体区分宿主细胞和病原体来源于它们结合病原体特异性表面糖的能力。最近,已经探索了使用聚糖结构作为疫苗佐剂/疫苗递送系统以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,除了提供对农场动物中先天免疫细胞- T细胞相互作用的更详细的理解之外,所提出的工作将为利用聚糖本身的澄清剂样性质提供基础,所述聚糖本身的澄清剂样性质是由其激活抗原呈递细胞上表达的炎症和吞噬受体的能力产生的。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之间存在实质性差异,以及它们识别的配体。这一观察结果对农场动物(特别是本文研究的反刍动物)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在其他哺乳动物种属中不起作用,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性的关键途径,从而减少AMR是改善目前的疫苗策略,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。
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Preliminary Volumetric Calculation of the Mucosal Surface in the Nares of Lambs Using a Segmentation of Computed Tomographic Images.
- DOI:10.3389/fvets.2020.620647
- 发表时间:2020
- 期刊:
- 影响因子:3.2
- 作者:Teeling KP;Werling D;Berner D
- 通讯作者:Berner D
CD23 is a glycan-binding receptor in some mammalian species
- DOI:10.1074/jbc.ra119.010572
- 发表时间:2019-10-11
- 期刊:
- 影响因子:4.8
- 作者:Jegouzo, Sabine A. F.;Feinberg, Hadar;Taylor, Maureen E.
- 通讯作者:Taylor, Maureen E.
Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality.
- DOI:10.3389/fimmu.2021.764390
- 发表时间:2021
- 期刊:
- 影响因子:7.3
- 作者:Bartens MC;Gibson AJ;Etherington GJ;Di Palma F;Holder A;Werling D;Willcocks S
- 通讯作者:Willcocks S
Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand.
- DOI:10.3389/fimmu.2023.1189587
- 发表时间:2023
- 期刊:
- 影响因子:7.3
- 作者:
- 通讯作者:
Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand 1
牛 C 型凝集素受体 Mincle 的表征和内源配体的潜在证据 1
- DOI:10.1101/2023.03.20.533273
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Holder A
- 通讯作者:Holder A
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Dirk Werling其他文献
WC1(+) gammadelta T cells indirectly regulate chemokine production during mycobacterium bovis infection in SCID-bo mice.
WC1( ) gammadelta T 细胞在 SCID-bo 小鼠牛分枝杆菌感染期间间接调节趋化因子的产生。
- DOI:
- 发表时间:
2009 - 期刊:
- 影响因子:4.3
- 作者:
A. Alvarez;J. Endsley;Dirk Werling;D. M. Estes - 通讯作者:
D. M. Estes
Therapeutic targeting of the innate immune system in domestic animals
- DOI:
10.1007/s00441-010-1054-9 - 发表时间:
2010-10-16 - 期刊:
- 影响因子:2.900
- 作者:
Tracey J. Coffey;Dirk Werling - 通讯作者:
Dirk Werling
TITLE: Analysis of Genetic Variation in the Bovine SLC11A1 Gene, Its Influence on the Expression of NRAMP1 and Potential Association With Resistance to Bovine Tuberculosis AUTHORS:
标题:牛 SLC11A1 基因遗传变异分析、其对 NRAMP1 表达的影响以及与牛结核病耐药性的潜在关联
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Angela Holder;Rachel Garty;Charlotte Elder;Paula Mesnard;Celine Laquerbe;Marie;M. Salavati;Muhammad Zubair Shabbir;Thomas Tzelos;Timothy Connelly;Bernardo Villarreal;Dirk Werling - 通讯作者:
Dirk Werling
Multi-omics analysis reveals regime shifts in the gastrointestinal ecosystem in chickens following anticoccidial vaccination and emEimeria tenella/em challenge
多组学分析揭示了鸡在抗球虫疫苗接种和柔嫩艾美耳球虫感染后胃肠道生态系统的转变。
- DOI:
10.1128/msystems.00947-24 - 发表时间:
2024-09-17 - 期刊:
- 影响因子:4.600
- 作者:
Po-Yu Liu;Janie Liaw;Francesca Soutter;José Jaramillo Ortiz;Fiona M. Tomley;Dirk Werling;Ozan Gundogdu;Damer P. Blake;Dong Xia - 通讯作者:
Dong Xia
Toll-like receptors in domestic animals
- DOI:
10.1007/s00441-010-1047-8 - 发表时间:
2010-10-07 - 期刊:
- 影响因子:2.900
- 作者:
Thomas W. Jungi;Katja Farhat;Iwan A. Burgener;Dirk Werling - 通讯作者:
Dirk Werling
Dirk Werling的其他文献
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{{ truncateString('Dirk Werling', 18)}}的其他基金
Protecting Pigs From Enzootic Pneumonia: Rational Design Of Safe Attenuated Vaccines.
保护猪免受地方性肺炎:安全减毒疫苗的合理设计。
- 批准号:
BB/X017540/1 - 财政年份:2023
- 资助金额:
$ 58.02万 - 项目类别:
Research Grant
22-ICRAD Call 2 Comparative host and species-specific immune responses of macrophages infected with zoonotic Leptospira interrogans
22-ICRAD Call 2 感染人畜共患问号钩端螺旋体的巨噬细胞的宿主和物种特异性免疫反应比较
- 批准号:
BB/X020061/1 - 财政年份:2023
- 资助金额:
$ 58.02万 - 项目类别:
Research Grant
Establishment of an Organ-on-a-chip facility for Veterinary Species
建立兽医物种器官芯片设施
- 批准号:
BB/X019675/1 - 财政年份:2023
- 资助金额:
$ 58.02万 - 项目类别:
Research Grant
Antimicrobials and improved diagnostics towards integrated control of CBPP
抗菌剂和改进的诊断以实现 CBPP 的综合控制
- 批准号:
BB/H009450/1 - 财政年份:2010
- 资助金额:
$ 58.02万 - 项目类别:
Research Grant
Aetiology pathogenesis and immunology of post-weaning multi-systemic wasting syndrome in pigs: genetic-environmental interactions
猪断奶后多系统消耗综合征的病因、发病机制和免疫学:遗传-环境相互作用
- 批准号:
BB/E018394/1 - 财政年份:2008
- 资助金额:
$ 58.02万 - 项目类别:
Research Grant
相似国自然基金
牛肌生成抑制素受体分子生物学特性研究
- 批准号:30972108
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- 资助金额:30.0 万元
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- 批准年份:2005
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
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