Metabolic reprogramming & inflammation: Fuelling the host response to pathogens.

Successful immune responses to pathogens rely on efficient host innate processes to contain and limit bacterial growth, induce inflammatory response and promote antigen presentation for the development of adaptive immunity. This energy intensive process is regulated through multiple mechanisms including receptor-mediated signaling, control of phago-lysomal fusion events and promotion of bactericidal activities. Inherent macrophage activities therefore are dynamic and are modulated by signals and changes in the environment during infection. So too does the way these cells obtain their energy to adapt to altered homeostasis. It has emerged recently that the pathways employed by immune cells to derive energy from available or preferred nutrients underline the dynamic changes associated with immune activation. In particular, key breakpoints have been identified in the metabolism of glucose and lipids which direct not just how cells derive energy in the form of ATP, but also cellular phenotype and activation status. Much of this comes about through altered flux and accumulation of intermediate metabolites. How these changes in metabolism directly impact on the key processes required for anti-microbial immunity however, is less obvious. Here, we examine the 2 key nutrient utilization pathways employed by innate cells to fuel central energy metabolism and examine how these are altered in response to activation during infection, emphasising how certain metabolic switches or 'reprogramming' impacts anti-microbial processes. By examining carbohydrate and lipid pathways and how the flux of key intermediates intersects with innate immune signaling and the induction of bactericidal activities, we hope to illustrate the importance of these metabolic switches for protective immunity and provide a potential mechanism for how altered metabolic conditions in humans such as diabetes and hyperlipidemia alter the host response to infection.