Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

Wculek, Stefanie K.; Heras-Murillo, Ignacio; Mastrangelo, Annalaura; Mañanes, Diego; Galán, Miguel Á.; Miguel, Verónica; Curtabbi, Andrea; Barbas, Coral; Chandel, Navdeep S.; Enrı́quez, José Antonio; Lamas, Santiago; Sancho, David

doi:10.1016/j.immuni.2023.01.011

Cited by 100 publications

(58 citation statements)

References 75 publications

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“…The analysis of MΦs and DCs in C. rodentium –infected Csf2 −/− mice refines previous reports and indicates responsiveness of DCs even in the absence of CSF2, whereas MΦs fail to expand and execute their antimicrobial activity because of impaired CSF2-dependent OXPHOS and mitochondrial ROS generation. This is in line with a recent report demonstrating OXPHOS as a distinguishing factor for proinflammatory MΦs, with impairment of OXPHOS leading to cellular stress and reduced MΦ numbers, particularly of alveolar MΦs that are also CSF2 dependent ( 61 , 62 ). Imprinting of these metabolic functions is predominant in monocytes and SAMs, pointing to a need to develop new tools to refine functional characterization of MΦs within distinct microanatomic locations.…”

Section: Discussionsupporting

confidence: 93%

Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling

et al. 2023

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Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism.

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Section: Discussionsupporting

confidence: 93%

Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling

et al. 2023

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“…The reason why 1-TbAd induces lipid accumulation specifically in M1 macrophages remains to be clarified. However, this apparent discrepancy could be linked to cell-specific differences in lipid handling and metabolism, since alveolar macrophages and M2 macrophages are committed to fatty acid oxidation, whereas M1 macrophages rely mainly on glycolysis for energy generation (21,22). Second, foamy macrophages observed during M. tuberculosis infection have often been reported to be filled with lipid droplets, a phenotype not observed in this study (16).…”

Section: Discussionmentioning

confidence: 64%

The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids

Rombouts¹

2023

Journal of Clinical Investigation

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Section: Current Limitati On S and Future Direc Tionsmentioning

confidence: 99%

“…The metabolic signature and functional response of macrophages is plastic and adapts to the tissue microenvironment, 183,184 which is difficult to mimic in an in vitro setting. A large variability in oxidative metabolism of macrophages within different tissues has already been observed under homeostatic conditions, 185 and this may be further increased in the context of disease. For example, in the chronic inflammatory setting of atherosclerosis, plaque macrophages are exposed to pro‐inflammatory cytokines, apoptotic cells and their releasate, and high levels of (oxidized) lipids and cholesterol, which can all affect their functional phenotype 186 .…”

Section: Current Limitations and Future Directionsmentioning

confidence: 99%

The role of efferocytosis‐fueled macrophage metabolism in the resolution of inflammation

Schilperoort

Ngai

Sukka

et al. 2023

Immunological Reviews

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SummaryThe phagocytosis of dying cells by macrophages, termed efferocytosis, is a tightly regulated process that involves the sensing, binding, engulfment, and digestion of apoptotic cells. Efferocytosis not only prevents tissue necrosis and inflammation caused by secondary necrosis of dying cells, but it also promotes pro‐resolving signaling in macrophages, which is essential for tissue resolution and repair following injury or inflammation. An important factor that contributes to this pro‐resolving reprogramming is the cargo that is released from apoptotic cells after their engulfment and phagolysosomal digestion by macrophages. The apoptotic cell cargo contains amino acids, nucleotides, fatty acids, and cholesterol that function as metabolites and signaling molecules to bring about this re‐programming. Here, we review efferocytosis‐induced changes in macrophage metabolism that mediate the pro‐resolving functions of macrophages. We also discuss various strategies, challenges, and future perspectives related to drugging efferocytosis‐fueled macrophage metabolism as strategy to dampen inflammation and promote resolution in chronic inflammatory diseases.

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Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

Cited by 100 publications

References 75 publications

Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling

Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling

The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids

The role of efferocytosis‐fueled macrophage metabolism in the resolution of inflammation

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