Volume 19 Issue 5, May 2019

A new study shows that immune activation after infection involves competition for energy with physiological programmes such as maintaining a normal body temperature. This trade-off favours immune tolerance as a strategy for host defence.

Doreen Cantrell describes a 2005 paper by Graham Hardie and colleagues showing that Ca²⁺–calmodulin-dependent protein kinase kinases could phosphorylate and activate AMPK, which suggested a biochemical link between T cell receptor signalling and ATP production.

Tumour cells induce membrane cholesterol efflux from macrophages, leading to macrophage acquisition of a pro-tumour phenotype.

During inflammation, IL-17 rewires metabolic processes in lymph node fibroblastic reticular cells, thereby supporting their survival and population expansion.

Liver macrophages produce the non-inflammatory factor IGFBP7, which has direct effects on liver metabolism in metabolic disease without requiring a switch to a pro-inflammatory phenotype.

During an immune response, macrophage metabolism is diverted to produce the metabolite itaconate, which has anti-inflammatory effects. This Review recounts the story of itaconate, from its discovery to its potentially far-reaching consequences for immunity, host defence and tumorigenesis.

As in other immune cells, the metabolic pathways in natural killer (NK) cells must be configured to meet the demands of their effector functions. This Review describes the specific metabolic requirements for NK cell responses and how defects in NK cell metabolism may contribute to NK cell dysfunction in chronic disease.

Different lineages of macrophages respond divergently to immune stimuli and microbial infection. This Review explores our current knowledge of how the different metabolic states of macrophage lineages impact the control or progression of intracellular bacterial infections.

The intestinal microbiota profoundly shapes host physiology through its production of small molecules and metabolites. Here, Honda and colleagues discuss how these microbial products shape immune function. They further consider the potential of ‘mining’ the microbiota for new microbial and metabolite-based immunotherapies.

In this Review, Erika Pearce and colleagues detail the metabolic changes that occur in the tumour microenvironment, explaining how these shape immune cell function at these sites. They highlight the potential of targeting these metabolic pathways to treat patients with cancer

B cells have many unique metabolic features. Markus Müschen highlights these in this Opinion article and proposes the concept of three key metabolic gatekeepers that protect against B cell-associated autoimmunity and lymphomas.