Grant: CIHR Fellowship

Macrophages are tissue-resident cells that fulfill homeostatic functions, notably in the central nervous system. Following assault, they become activated and secrete mediators that lead to a local inflammation (neuroinflammation). Moreover, large numbers of infiltrating macrophages exert inflammatory effects that contribute to neuroinflammation. Even though resident and infiltrating macrophages may have differing immunological functions and roles, these are dependent on their metabolism (a phenomenon called immunometabolism). As such, metabolic reprogramming can modulate macrophage functions, and subsequently their role, including their inflammatory activities and participation in the development of disease. While controlled inflammation is required to resolve an assault and repair damage, its exacerbation can result in permanent damage and debilitating disabilities. Indeed, exacerbated neuroinflammation is responsible for numerous life-threatening diseases whose burden on human health in Canada is extensive. However, information regarding the contribution to neuroinflammation of macrophage immunometabolic reprogramming remains largely unknown. Consequently, the goal of this project is to study this contribution using a mouse model of experimental autoimmune encephalomyelitis. Firstly, the metabolic processes of resident and infiltrating macrophages modulated during neuroinflammation, in comparison with homeostasis, will be identified. Thereafter the role of this reprogramming on the immunological functions of macrophages will be evaluated using cells isolated from mice deficient for key metabolic pathways and/or specific checkpoints previously identified. Finally, the contribution of macrophage immunometabolic reprogramming to neuroinflammation and the development of and outcome of disease will be assessed using these same deficient mice. In summary, this project aims to dissect the contribution to neuroinflammation of macrophage immunometabolic reprogramming