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

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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.