How inflammatory resolution shapes long-term tissue immunity

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Inflammation is a protective response to infection and injury. However, once its job is done it's imperative that inflammation then switches off. This can be best exemplified by a bee sting where skin becomes hot, red, swollen and painful, the so-called four cardinal signs of inflammation. However, within hours or certainly a day, the heat, redness, swelling and pain goes away. This latter process is called inflammatory resolution. Importantly, resolution of acute inflammation is a natural sequence of events that, until now, was believed to lead the affected tissues back to the physiological and immunological state they experienced before inflammation occurred. However, we propose that this is not the case, and that resolution triggers a series of local clinically silent, but immunologically active events that are essential for maintaining the long-term immune health and well-being of the infected/damaged tissue. The aim of this proposal, therefore, is to study these novel post-inflammatory resolution processes and understand how they immunologically enhance tissues for prolonged and improved immune protection. The experiments proposed here will describe a new area of immune activity that extends long after the outwards sign of heat, redness, swelling and pain have resolved with a key role in maintaining lifelong heathy ageing and well-being in terms of shaping more efficient responses to secondary and subsequent infections. Consequently, it will describe new immune processes whose dysregulation arising from old age, pathogenic infections, environmental influences may become dysregulated driving aberrant immune responses and shortening human and animal life span. Consequently, we envision using this knowledge to optimise immune responses to infection without the need for antimicrobials and the problems of antimicrobial resistance.