Mitochondrial metabolism, reactive oxygen species, and macrophage function-fishing for insights.

ABSTRACT

Metabolism and defense mechanisms that protect against pathogens are two fundamental requirements for the survival of multicellular organisms. Research into metabolic disease has revealed these core mechanisms are highly co-dependent. This emerging field of research, termed immunometabolism, focuses on understanding how metabolism influences immunological processes and vice versa. It is now accepted that obesity influences the immune system and that obesity-driven inflammation contributes to many diseases including type 2 diabetes, cardiovascular disease and Alzheimer's disease. The immune response requires the reallocation of nutrients within immune cells to different metabolic pathways to satisfy energy demands and the production of necessary macromolecules. One aspect of immunometabolic research is understanding how these metabolic changes help regulate specific immune cell functions. It is hoped that further understanding of the pathways involved in managing this immunological-metabolic interface will reveal new ways to treat metabolic disease. Given their growing status as principle drivers of obesity-associated inflammation, monocytes/macrophages have received much attention when studying the consequences of inflammation within adipose tissue. Less is known regarding how metabolic changes within macrophages (metabolic reprogramming) influence their immune cell function. In this review, we focus on our current understanding of how monocytes/macrophages alter their intracellular metabolism during the immune response and how these changes dictate specific effector functions. In particular, the immunomodulatory functions of mitochondrial metabolism and mitochondrial reactive oxygen species. We also highlight how the attributes of the zebrafish model system can be exploited to reveal new mechanistic insights into immunometabolic processes.