Metabolism can be broadly divided into anabolic, energy-consuming, biosynthetic processes and energy-generating catabolic processes. Different biological functions rely on primarily catabolic or primarily anabolic metabolism. The field of immunometabolism has advanced our understanding of how allocation of metabolic resources (energy and metabolites) supports host defenses. On cellular, tissue, and organismal levels, emerging evidence demonstrates a complex interplay between metabolism and inflammation that must be precisely regulated to support biological functions. It is now well established that inflammatory signals tend to activate anabolic processes necessary to support immune responses. Additionally, macrophages, dendritic cells, and T cells can undergo metabolic reprogramming to support different types of cellular functions and activities; thus, naïve and memory T cells rely on catabolic metabolism, whereas effector T cells and macrophages stimulated through Toll-like receptors engage in glycolysis and anabolic metabolism. In addition, at least some anti-inflammatory signals promote metabolic programs that are not supportive of the inflammatory response. The dysregulation of these processes underlies many modern human diseases such as sepsis, diabetes, and obesity.

We apply evolutionary and ecological principles of life history to discuss the recent advances in immunometabolism within a unifying framework. From this perspective, we highlight the parallels between cellular and systemic control of metabolism. According to life history theory, biological programs can be broadly divided into growth, reproduction, and maintenance. The choice among these programs is dictated by the quality of the environment. Thus, favorable environments promote growth and reproduction, whereas hostile environments promote maintenance and survival programs. These life history programs operate at both organismal and cellular levels. At the organismal level, different hypothalamic-pituitary axes control the engagement of metabolic programs that support organismal growth, reproduction, and maintenance. At the cellular level, activated and quiescent states also broadly correspond to cellular growth and reproduction (proliferation) versus maintenance (quiescence), respectively.

We propose that maintenance programs can be further subdivided into defense and dormancy. This is because the environment can be hostile for two different reasons: It can lack what an organism needs (nutrients and other resources), or it may have what an organism does not want (pathogens, predators, toxins, etc.). Dormancy and defense deal with these two types of hostile environments, respectively. Dormancy (or quiescence) is an energy-preserving state that permits survival in the face of nutrient scarcity. Defenses, on the other hand, are energy-consuming processes that protect from hostile factors, such as pathogens. We then apply these concepts to immunometabolism and highlight important implications for the logic behind the coordination of cellular function with corresponding metabolic programs.

Dysregulation of metabolism and inflammation is a common feature of most of the prevalent modern human diseases. Understanding the complex cellular, tissue, and organismal biology that drive disease pathogenesis is an urgent need. The conceptual framework presented here highlights the logic of metabolic control and the parallels between systemic and cellular metabolism; moreover, it illuminates important areas of exploration in the fields of neuroendocrinology, metabolism, and inflammation biology.