Metabolism of tissue macrophages in homeostasis and pathology

Abstract

Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural components. The emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune cells. Macrophages are embryo- or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome, atherosclerosis, fibrosis or cancer. Macrophage metabolism has largely been studied in vitro. However, different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific functions. This context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological conditions. Here, we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases.

Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

“…The switch from mitochondrial respiration to glycolysis is crucial for the inflammatory response in monocytes, macrophages and dendritic cells (28, 37). Pnpt1 knockout induces metabolic reprogramming by decreasing oxidative phosphorylation and increasing glycolysis (38).…”

“…LPS stimulation induces a glycolytic shift through downregulation of mitochondrial respiration and increasing glycolytic gene expression. This glycolytic shift provides rapid ATP production, and generates nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) to protect cells from the production of excess ROS (28, 29). Both NLRP3 and its critical binding partner, NIMA-related kinase 7 (NEK7) are regulated by ROS (30, 31), suggesting that macrophage metabolic reprogramming could regulate NLRP3 inflammasome activation.…”

Spectral flow cytometry reveals metabolic heterogeneity in tissue macrophages

“…Each tissue-niche has its own controlled metabolic microenvironment (Wculek et al ., 2021). Mphs are therefore predicted to have complementary metabolic wiring to support their habitation in any particular tissue (Bleriot et al ., 2021; Bonnardel et al, 2019; Davies et al, 2017; Svedberg et al ., 2019).…”

“…The Hp-driven increases in GLUT1 and CD36 in intestinal mphs support previously ascribed needs for glucose and fatty acids of mphs in the context of type 2 immunity (Huang et al ., 2014; Huang et al, 2016). Conversely, fatty acid oxidation is frequently cited as a requirement for alternative activation (Wculek et al ., 2021), yet we see no evidence of altered CPT1A expression in activated, duodenal mphs during Hp infection. The role of fatty acid oxidation for in vitro polarization has already been questioned (Divakaruni et al, 2018; Nomura et al, 2016), and here we make further observations in support of this argument in vivo .…”

In Vitro Immunomodulatory Effects of Inonotus obliquus Extracts on Resting M0 Macrophages and LPS-Induced M1 Macrophages

“…Macrophages are bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome [ 24 ]. Broadly, a macrophage is divided into three phenotypes: M0, M1-like, and alternative activated macrophage (M2)-like [ 23 ].…”