Content area
Full Text
R E V I E W S
Most immunologists have a distant memory of learning metabolic pathways as undergraduates. Many of these proto-immunologists saw these pathways as scientifically interesting but unlikely to impinge on their own growing research interests into the complexity of the immune response. Equally, those scientists who became immunologists later were largely unaware of how metabolic pathways might be of direct relevance to their research, unless they had a particular interest in the role of immune cells in obesity or in metabolic diseases, such as type 2 diabetes. Of course there was a minority of immun ologists who were considering metabolic processes in the functioning of immune cells, with early studies from more than 30years ago describing the requirement of certain metabolites for macrophage, neutrophil and Tcell function14. These studies largely focused on energy production and biosynthesis, as activated macrophages or rapidly dividing Tcells have huge metabolic demands. There was also a major interest in mechanistic target of rapamycin (mTOR), which is a central metabolic regulator of immunity5, and AMP kinase. mTOR is the catalytic subunit of two distinct complexes mTOR complex 1 (mTORC1) and (mTORC2) that can sense amino acids and growth factors and promote mRNA translation and lipid synthesis to support cell growth; beyond this, mTOR signalling regulates numerous events that are crucial for Tcell and monocyte differentiation6. AMP kinase (which is activated during nutrient deprivation) promotes catabolism (for example, of fatty acids) and also inhibits mTOR activity, thereby limiting immune cell activation7.
What we have seen in the past five years or so is something of a rediscovery of metabolism by immunologists and the emergence of what is now termed the
field of immunometabolism. Why did this happen? Technological advances have helped tremendously; highly sensitive metabolomic approaches allow us to define the alterations in metabolites that occur during immune cell activation and show how metabolites are directly linked to immune cell effector functions. Immunology itself as a science has advanced hugely in the past 30years. Notable advances include the discovery of whole new immune receptor systems (most notably the pattern recognition receptors (PRRs)), the description of many cytokines and immune cell types, and a deeper understanding of the development and molecular regulation of these immune cells. Furthermore, we...