Adaptation

Adaptive behaviors in hematopoietic cells can promote homeostasis and enhance immune responses to pathogens, but they can also perpetuate the chronicity of inflammatory or metabolic disorders.

In this Review, Natoli and Ostuni discuss the mechanisms of adaptation and memory in immunity, with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.

In this Review, Pearce and colleagues discuss the metabolic adaptation of immune cells to various tissues and how functional adaptation compared with maladaptation within the niche can affect tissue homeostasis.

In this Review, Chavakis and colleagues discuss the mechanisms that govern the adaptation of hematopoietic progenitor cells to inflammation and its effects on the pathogenesis of human disease.

Edelson and colleagues show that the transcription factor Bhlhe40 is required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages, but not that of other tissue-resident macrophages.

Succinate is a signaling metabolite sensed extracellularly by SUNCR1. Fernandez-Veledo and colleagues show that activation of SUCNR1 promotes an anti-inflammatory phenotype in adipose-tissue macrophages in lean mice and people.

Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.

Regulatory T cells obstruct effective anti-cancer immune responses. Vignali and colleagues demonstrate that IL-10 production and IL-35 production by tumor-infiltrating regulatory T cells mediate differential and non-redundant suppressive effects on tumor-reactive cytotoxic T cells.

Control of macrophage activation in the lungs is essential for the prevention of tissue damage. MacDonald and colleagues show that alveolar macrophages have impaired glycolysis and are hyporesponsive during type 2 inflammation in a manner controlled by the lung environment.

Muscle damage elicits a sterile immune response that facilitates complete regeneration. Nagy and colleagues map the mediator lipidome during the transition from inflammation to resolution in skeletal muscle injury.

Neutrophils rapidly respond to bacterial and fungal infections but can cause substantial collateral tissue damage if not restrained. Rosenbauer and colleagues show that the transcription factor PU.1 serves a cell-intrinsic role to prevent over-exuberant neutrophil responses to fungal infection.

The skin and intestine are unique environments at the front line of the immune system. Powrie and colleagues review the distinctive adaptations acquired by regulatory T cells at these barrier surfaces.

The role of IFN-λ in adaptive immunity is not well characterized. Staeheli and colleagues show that in the lungs, IFN-λ elicits production of the cytokine TSLP from M cells and that this in turn is essential for effective adaptive immunity and control of infection with influenza virus.

Macrophages can shift their cellular metabolism in response to tissue cues and infection. Pearce and colleagues show that lipopolysaccharide-activated ‘inflammatory’ macrophages become depleted of NAD⁺ pools and require the salvage-pathway enzyme NAMPT to sustain cellular redox balance.

Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.

Epelman and colleagues use fate mapping and single-cell transcriptomics to describe the dynamics of resident and recruited cardiac macrophages during ischemic injury.

DEL-1 protein interferes with leukocyte adhesion to prevent inflammation. Chavakis and colleagues now show that DEL-1 contributes to tissue resolution after inflammation by promoting macrophage-mediated efferocytosis and M2-like pro-resolving activities.

Macrophages alter their metabolism in response to infection. The authors show that resting macrophages generate nicotinamide adenine dinucleotide via de novo synthesis, but activated and aged cells suppress the rate-limiting enzyme quinolinate phosphoribosyltransferase to regulate mitochondrial and immunological functions.

Tissue-resident memory cells are functionally distinct from lymph node memory cells. Randall and colleagues show that lung infection establishes B cell memory in situ and confers superior responses following challenge infection, which will inform vaccine design for respiratory viruses.