Understanding mucosal immunology and co-infections in the chicken to drive vaccine strategies. – MICHIC

Despite the fact that vaccine use in poultry is greater than in any other farmed species,
the mechanisms by which they induce protection, particularly at mucosal surfaces, are
poorly understood. Many diseases constraining avian productivity and welfare affect the
respiratory tract and are multi-factorial. A better understanding of responses in the
respiratory tract to bacterial and viral infections, co-infections and vaccines is needed to
control endemic production diseases.
Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease,
threatening food security and avian welfare at a time of increasing global demand.
Infections frequently involve sepsis, inflammation of visceral organs and reduced egg
yield/quality, with losses through early mortality, reduced productivity and product
condemnation. The expansion of free-range production systems will increase the incidence
of colibacillosis through greater exposure of birds to environmental pathogens, stress and
injury associated with forming a social hierarchy. Importantly, APEC infections are
frequently associated with respiratory viral infections.
The nature and consequences of host-pathogen interactions during APEC (co-)infections
are poorly understood. Virulence factors of APEC, antagonistic or synergistic effects of
co-infection and the basis of immunity and resistance are ill-defined. The EC-wide ban on
prophylactic antibiotic use and transmissible resistance render poultry susceptible to APEC
infection. Existing vaccines confer limited serogroup-specific protection.
This project will advance understanding of mucosal immune responses in the avian
respiratory tract. It will provide a comprehensive description of the respiratory tract
immune system, leading to new tools to study immune responses and improved
understanding of the mechanism and site of antigen presentation in the lung. We will
thereby identify correlates of resistance and susceptibility to, and the impact of viral
infections on the outcome of, APEC infection. Using transgenic chickens we will further
characterise the role of antigen-presenting cells and humoral immunity during APEC
infection and vaccination, for example by using our unique MacRed chickens (in which all
cells of the mononuclear phagocyte lineage (macrophages, monocytes and dendritic cells)
express a fluorescent protein driven by the chicken CSF-1 receptor), and immunoglobulin
knock-out chickens (which lack the B cell receptor and thus antibody).