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

尽管有抗菌剂和疫苗，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抗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尤其具有挑战性，因为一些细菌可以在适当的环境下生活在牲畜中而不会造成任何有害影响(例如，鸡只中的沙门氏菌或弯曲杆菌)，但仍会对人类造成疾病。这种特定物种的细菌“耐受性”是如何发生的还不清楚，这使得控制策略的设计变得困难。疫苗接种策略已经降低了一些细菌的发病率，但目前的许多疫苗并不理想。对抗家畜传染病的替代方法是使用选择性育种来抵抗疾病，或者产生转基因动物来改变它们对感染的敏感性。在不同物种的哺乳动物和鸟类之间，PRR的谱系及其检测到的细菌存在重大差异。我们以前的BBSRC资助的研究发现，一些PRR，特别是鸡缺失的节点样受体(NLRs)NLRC4和NOD2，是抗沙门氏菌免疫反应的重要调节因子。通过对小鼠和鸡细胞的比较研究，这笔赠款将确定驱动宿主对感染反应的NLR信号通路。

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.