Effects of Nod-like receptor activity on protective immunity against Salmonella infection

Nod样受体活性对沙门氏菌感染保护性免疫的影响

• 批准号: BB/K006436/1
• 负责人: Clare Bryant
• 金额: $ 94.83万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK006436%2F1
• 关键词: Effects; Nod; like; receptor; activity

Infectious diseases remain major problems with significant economic and social impact despite the availability of antimicrobials and vaccines. The development of resistance to antimicrobials by microorganisms means that alternative control measures are required. Control of food-borne bacterial infections that infect people is particularly challenging because some bacteria can live in livestock without causing any harmful effects under the right circumstances (for example species of Salmonella enterica or Campylobacter in chickens) yet cause disease in humans. How this species-specific bacterial "tolerance" occurs is not understood which makes design of control strategies difficult. Vaccination strategies have reduced disease incidence for some bacteria, but many current vaccines are not ideal. Alternative approaches to combat infectious disease in livestock are to use selective breeding for disease resistance or to generate genetically modified animals to alter their susceptibility to infection. To design suitable control strategies it is essential to understand how bacteria co-exist with livestock.Bacteria are recognised in humans and animals by specialised proteins called pattern recognition receptors (PRRs) to activate anti-bacterial immunity. There are major differences in the repertoires of PRRs and in the bacteria they detect between different species of mammals and birds. Our previous BBSRC funded research has found that some of the PRRs specifically the Nod Like Receptors (NLRs) NLRC4 and Nod2, that are missing from chickens, are important regulators of immune responses against Salmonella. Using comparative studies between mouse and chicken cells this grant will identify the NLR-signalling pathways driving the host response to infection. By expressing human NLRC4 or Nod2 in chicken cells and in chickens we will determine whether these PRRs contribute to why humans and animals react differently to the same salmonellae.

尽管有抗微生物剂和疫苗，传染病仍然是具有重大经济和社会影响的主要问题。微生物对抗菌剂产生耐药性意味着需要采取替代控制措施。控制感染人类的食源性细菌感染特别具有挑战性，因为有些细菌可以在适当的情况下生活在牲畜中而不会造成任何有害影响（例如鸡中的沙门氏菌或弯曲杆菌），但会导致人类疾病。这种物种特异性细菌“耐受性”是如何发生的尚不清楚，这使得控制策略的设计变得困难。疫苗接种策略降低了某些细菌的发病率，但目前许多疫苗并不理想。防治牲畜传染病的替代办法是利用选择性育种以获得抗病能力，或培育转基因动物以改变其对感染的敏感性。要设计合适的控制策略，必须了解细菌如何与牲畜共存。人类和动物通过称为模式识别受体（PRRs）的特殊蛋白质识别细菌，以激活抗菌免疫力。在不同种类的哺乳动物和鸟类之间，PRR的所有组成部分和它们检测到的细菌存在重大差异。我们之前的BBSRC资助的研究发现，一些PRR，特别是鸡中缺失的Nod样受体（NLR）NLRC 4和Nod 2，是抗沙门氏菌免疫反应的重要调节因子。利用小鼠和鸡细胞之间的比较研究，该基金将确定驱动宿主对感染反应的NLR信号通路。通过在鸡细胞和鸡中表达人NLRC 4或Nod 2，我们将确定这些PRR是否有助于为什么人类和动物对相同的鲑鱼产生不同的反应。

项目成果

Mitochondrial damage contributes to Pseudomonas aeruginosa activation of the inflammasome and is downregulated by autophagy.

• DOI: 10.4161/15548627.2014.981915
• 发表时间: 2015
• 期刊: Autophagy
• 影响因子: 13.3
• 作者: Jabir MS;Hopkins L;Ritchie ND;Ullah I;Bayes HK;Li D;Tourlomousis P;Lupton A;Puleston D;Simon AK;Bryant C;Evans TJ
• 通讯作者: Evans TJ

Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.

• DOI: 10.1016/j.celrep.2021.109614
• 发表时间: 2021-08-24
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Digby Z;Tourlomousis P;Rooney J;Boyle JP;Bibo-Verdugo B;Pickering RJ;Webster SJ;Monie TP;Hopkins LJ;Kayagaki N;Salvesen GS;Warming S;Weinert L;Bryant CE
• 通讯作者: Bryant CE

Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

• DOI: 10.1186/s40168-016-0159-0
• 发表时间: 2016-04-05
• 期刊: Microbiome
• 影响因子: 15.5
• 作者: Falcone EL;Abusleme L;Swamydas M;Lionakis MS;Ding L;Hsu AP;Zelazny AM;Moutsopoulos NM;Kuhns DB;Deming C;Quiñones M;Segre JA;Bryant CE;Holland SM
• 通讯作者: Holland SM

The TLR4 D299G and T399I SNPs are constitutively active to up-regulate expression of Trif-dependent genes.

• DOI: 10.1371/journal.pone.0111460
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hold GL;Berry S;Saunders KA;Drew J;Mayer C;Brookes H;Gay NJ;El-Omar EM;Bryant CE
• 通讯作者: Bryant CE

The frequency and duration of Salmonella-macrophage adhesion events determines infection efficiency.

• DOI: 10.1098/rstb.2014.0033
• 发表时间: 2015-02-05
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Achouri S;Wright JA;Evans L;Macleod C;Fraser G;Cicuta P;Bryant CE
• 通讯作者: Bryant CE