Specific and Complex Reprogramming of Cellular Metabolism in Myeloid Cells during Innate Immune Responses

Abstract

Renewed interest in immune cell metabolism has led to the emergence of a research field aimed at studying the importance of metabolic processes for an effective immune response. In addition to the adaptive immune system, cells of the myeloid lineage have been shown to undergo robust metabolic changes upon activation. Whereas the specific metabolic requirements of myeloid cells after lipopolysaccharide/TLR4 stimulation have been extensively studied, recent evidence suggested that this model does not represent a metabolic blueprint for activated myeloid cells. Instead, different microbial stimuli, pathogens, or tissue microenvironments lead to specific and complex metabolic rewiring of myeloid cells. Here we present an overview of the metabolic heterogeneity in activated myeloid cells during health and disease. Directions for future research are suggested to ultimately provide new therapeutic opportunities. The uniqueness of metabolic signatures accompanying different conditions will require tailor-made interventions to ultimately modulate aberrant myeloid cell activation during disease.

Activation of the sympathetic nervous system modulates neutrophil function

“…Emerging research indicates that cellular metabolic pathways serve three major functions: generation of energy, production of building blocks necessary for cellular maintenance and proliferation, and modulation of cellular signaling. Evidence also indicates that the metabolic alterations in myeloid cells differ depending on the type of stimulus, immune context, and tissue microenvironment . Our findings of NA‐induced metabolic activity in neutrophils at the same time as impaired chemotaxis raise the possibility that activation of ARs on neutrophils results in decreased effector function via effects on cellular metabolism.…”

“…Evidence also indicates that the metabolic alterations in myeloid cells differ depending on the type of stimulus, immune context, and tissue microenvironment. 57 Our findings of NA-induced metabolic activity in neutrophils at the same time as impaired chemotaxis raise the possibility that activation of ARs on neutrophils results in decreased effector function via effects on cellular metabolism. To our knowledge, this is the first report of enhanced metabolic activity induced by the activation of SNS in the modulation of neutrophil function.…”

A novel strategy for single-cell metabolic analysis highlights dynamic changes in immune subpopulations

“…Analysis of monocytes, which play a key role in innate immune function, revealed a higher expression of all metabolic proteins relative to other cell types. This suggests that they exist in a metabolically poised state with implications for inflammatory responses and plasticity 48,49 . This elevated expression was not due to assay intrinsic factors such as cellular size, as the mDC and monocyte populations share a similar forward scatter profile, yet their metabolic protein expression is vastly different (data not shown).…”

Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

“…Trained innate immunity has previously been documented to be induced by BCG immunization [73], and has recently been suggested to be the mechanism underlying the association between previous bacterial and fungal infections and the development of atherosclerosis [74, 75]. In these models, trained immunity and epigenetic reprogramming is driven in part from a switch from oxidative phosphorylation to increased aerobic glycolysis [76, 77]. In the case of BCG, trained circulating monocytes can be found months after immunization, which strongly suggests reprogramming of bone marrow progenitors [78].…”