Metabolism and lipid mediators as regulators of innate immune cell function: implications for inflammation and immune responses

Abstract

Innate immune cells, such as macrophages and dendritic cells, acquire certain metabolic profiles to support their immune functions. Additionally, these cells also produce lipid mediators – lipid-derived molecules that act as chemical messengers and help direct the cellular function of the cells themselves and other neighbouring immune cells.

In this thesis I explored both of these topics and looked into how cellular metabolism and lipid mediators control the immune function of macrophages and dendritic cells – two types of innate immune cells – in the context of chronic inflammatory diseases, such as the autoimmune disease rheumatoid arthritis, and in the context of infectious diseases, such as SARS-CoV-2 and helminth infections.

We showed that, to support the inflammatory response, macrophages and dendritic cells can tap into different metabolic pathways in response to the same pro-inflammatory stimulus, and that macrophages can tap into different metabolic pathways in response to different pro-inflammatory stimuli. We were also able to explore the complex role of lipid mediators downstream of cyclooxygenase-2 and how the same lipid mediator can lead to different types of inflammatory response in some contexts or be dispensable in other contexts.