PIGIMMUNITY

The pig industry is facing an increasing number of challenges, in the perspective of a sustainable and safe food production. By 2050, the world population is expected to increase to more than 9 billion people and the demand for animal protein will at least double. Increased food production gains have been achieved largely by livestock intensification, with intensive farms becoming more dependable on antibiotics for disease prevention and treatments. This has led to the emergence of new antibiotic-resistance bacteria and, subsequently, increased therapeutic failure. An example is the increased trend in antibiotic resistance of Actinobacillus pleuropneumoniae (A.pp.), the causative agent of porcine pleuropneumonia. New legislation and programs have been set up to reduce antibiotic use and the apparition of antibiotic resistances. However, there is the risk of increase disease incidence, with great economic costs. Stimulation of innate immunity has been identified as a promising prophylactic and/or therapeutic strategy to combat infectious diseases due to their ability to activate host immune mechanisms with a broad spectrum of protection. In this regard, flagellin, an agonist of Toll-like receptor 5 (TLR5), receptor of the innate immune system, emerges as a possible alternative strategy to increase resistance to both respiratory and intestinal diseases. This protection seem to be linked to a pro-inflammatory activity of flagellin that promotes the recruitment and maturation of immune cells, therefore preparing the mucosal environment for the arriving bacteria. At the same time, flagellin pre-treatment seems to reduce tissue damage, promoting full resolution of the process. Understanding this process will serve to develop better and safer strategies that combine high level of protection to infection whilst avoiding exacerbated inflammation, which will lead to a reduction in the use of antibiotics. PIGIMMUNITY proposes a systems biology approach to determine the factors that control flagellin-induced modulation of the immune system and resistance to disease. Single cell studies, mathematical modelling and in vivo evaluation of the protective effect of flagellin will be combined to improve our understanding of the mechanisms underlying flagellin protection against pathogens. The project will generate comprehensive knowledge on the mechanisms that regulate pig innate immunity, more specifically TLR5 signalling. It will identify new pathways and molecular targets that enhances pig immunity and resistance to disease. This approach will serve to develop better and safer therapies that combines high level of protection to infection whilst avoiding exacerbated inflammation, improving production yields and pig industry competitiveness. It will also help to decrease the use of antibiotics, and, therefore, its environmental residues, contributing to the reduction of the development of antibiotic resistances.