Mitochondrial choline metabolism in innate immunity

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Choline is a nutrient that plays an important role in all cells. Our research wants to understand how aspects of immunity and metabolism are linked. Immune cells called macrophages are constantly surveying for an immune trigger such as bacteria or damaged cells. When they see a trigger, they can turn on specific programs that are meant to either control an infection or repair cellular damage. We have shown that macrophage cells can become over-activated and inflammatory (angry) when choline cannot be taken into the cell (which might actually be good for something like infection). On the flip side, when these cells encounter an immune trigger, they up-regulate choline transport and metabolism (which again, might be a necessary process). This has been the focus of our previous NSERC-funded work. But we do not think that is the whole story. Choline is made into membranes in all types of cells and this is a big part of its importance. Choline can also enter the powerhouse of the cell (mitochondria) where it can then affect how DNA is read and interpreted, but this was only thought to happen in the liver and kidney. Based on new evidence from our lab and others, we think that choline can enter and be processed in the mitochondria of immune cells, but how, why and when this happens is still a mystery. We are aiming to test 1) how macrophage cells take up choline into their mitochondria, 2) if/how this special uptake of choline into the mitochondria can change with different immune triggers and 3) what are the overall consequences of this process (what pathways and processes are affected). We have uncovered an important role for choline metabolism in controlling inflammation and vice versa. However, our recent observations that choline is taken into the mitochondria of immune cells has identified a previously unexplored and unanticipated pathway in these important cells. This basic discovery-based research could highlight a new regulator of immune cells and extend our understanding of how the immune system and metabolism are linked.