The world is inhabited by more than 7.6 billion people, of whom one in nine suffer chronic undernourishment or starvation. How this ‘nutrient-restricted’ situation affects immune function had not, until recently, been investigated. Indeed, little thought had been given to how the biochemical changes that occur under conditions of nutrient stress translate to fundamental changes in immune cells and their capacity to generate antibodies or effector and memory cells for protection. A study published by Iyer et al. in 2012 changed all that.

Although it had already been recognized that malnutrition is associated with poor vaccine responses, Iyer et al. linked cellular nutrient levels in immune cells to the ability of cytotoxic T cells to mount a vigorous response to a challenge. The group discovered that chronic malnutrition limited the ability of the immune system to either replenish key cellular compartments through homeostatic proliferation or recruit antigen-specific memory T cells into a secondary response, two essential functions that are required for long-lived immune protection. Thus, the fate of immune cells — in this case, CD8+ T cells — is strongly determined by their metabolism, which directly influences immune health. The study also showed that immune cell metabolism depends on the protein and energy supplies in the diet and that this could be manipulated to improve immune outcomes.

the fate of immune cells … is strongly determined by their metabolism

The work of Iyer et al. provided a first clue to how different metabolic products in cells affect their development, maintenance and protective functions. In exciting developments extending from this landmark paper, it is now recognized that the metabolic and signalling requirements of T cells are interlinked. This affects both T cell fate and their capacity to reprogramme their functions to deal with particular types of infection. The metabolic programme of immune cells has also been found to influence the outcome of diseases such as obesity, diabetes and cancer. The oversupply of nutrients also affects immune cell function and can itself contribute to different types of disease. Collectively, these studies have led to an entirely new direction in immunological research. Emerging exciting questions will impact our understanding not only of immune cell function, but also of disease processes, and potentially uncover new therapeutic leads for treatment.