Metabolic influence on macrophage polarization and pathogenesis

Thapa, Bikash Bikram; Lee, Keunwook

doi:10.5483/bmbrep.2019.52.6.140

Cited by 149 publications

(143 citation statements)

References 142 publications

(132 reference statements)

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“…Exposure of human monocytes to C. albicans , β-glucan and LPS triggers an increase in glycolysis, lactate secretion and ROS production [ 28 , 45 ]. Similarly, metabolic changes underpin polarization of macrophages, either to pro-inflammatory M1 or protective M2 [ 46 ]. M1 macrophages are highly glycolytic, have limited oxidative phosphorylation and increased flux via the pentose phosphate pathway, while M2 macrophages rely on the TCA cycle and oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Monitoring Glycolysis and Respiration Highlights Metabolic Inflexibility of Cryptococcus neoformans

Lev

Desmarini

et al. 2020

Pathogens

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Cryptococcus neoformans is a human fungal pathogen that adapts its metabolism to cope with limited oxygen availability, nutrient deprivation and host phagocytes. To gain insight into cryptococcal metabolism, we optimized a protocol for the Seahorse Analyzer, which measures extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) as indications of glycolytic and respiratory activities. In doing so we achieved effective immobilization of encapsulated cryptococci, established Rotenone/Antimycin A and 2-deoxyglucose as effective inhibitors of mitochondrial respiration and glycolysis, respectively, and optimized a microscopy-based method of data normalization. We applied the protocol to monitor metabolic changes in the pathogen alone and in co-culture with human blood-derived monocytes. We also compared metabolic flux in wild-type C. neoformans, its isogenic 5-PP-IP5/IP7-deficient metabolic mutant kcs1∆, the sister species of C. neoformans, Cryptococcus deuterogattii/VGII, and two other yeasts, Saccharomyces cerevisiae and Candida albicans. Our findings show that in contrast to monocytes and C. albicans, glycolysis and respiration are tightly coupled in C. neoformans and C. deuterogattii, as no compensatory increase in glycolysis occurred following inhibition of respiration. We also demonstrate that kcs1∆ has reduced metabolic activity that correlates with reduced mitochondrial function. Metabolic inflexibility in C. neoformans is therefore consistent with its obligate aerobe status and coincides with phagocyte tolerance of ingested cryptococcal cells.

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Section: Discussionmentioning

confidence: 99%

Monitoring Glycolysis and Respiration Highlights Metabolic Inflexibility of Cryptococcus neoformans

Lev

Desmarini

et al. 2020

Pathogens

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“…Interestingly, the authors also found that etomoxir was able to inhibit M2 polarization in both control and Cpt2-deficient BMDM, which suggests that the data based on the use of etomoxir must be taken with caution, since it is possible that CPT1 has other functions outside FAO or that etomoxir is not specific for CPT1 (51). Divakaruni et al further supported this by showing that etomoxir has off-target effects indeed and that the inhibition of M2 polarization by this compound happens through the alteration of CoA levels rather than the inhibition of fatty acid oxidation (52). Overall, the available data suggest that the role of FAO in macrophage polarization is more complicated than initially thought.…”

Section: Dual Role Of Lipid Metabolism In Macrophage Polarizationmentioning

confidence: 99%

New Insights on the Role of Lipid Metabolism in the Metabolic Reprogramming of Macrophages

et al. 2020

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Macrophage activation is intimately linked to metabolic reprogramming. Inflammatory (M1) macrophages are able to sustain inflammatory responses and to kill pathogens, mostly by relying on aerobic glycolysis and fatty acid biosynthesis. Glycolysis is a fast way of producing ATP, and fatty acids serve as precursors for the synthesis of inflammatory mediators. On the opposite side, anti-inflammatory (M2) macrophages mediate the resolution of inflammation and tissue repair, switching their metabolism to fatty acid oxidation and oxidative phosphorylation. Over the years, this classical view has been challenged by recent discoveries pointing to a more complex metabolic network during macrophage activation. Lipid metabolism plays a critical role in the activation of both M1 and M2 macrophages. Recent evidence shows that fatty acid oxidation is also essential for inflammasome activation in M1 macrophages, and glycolysis is now known to fuel fatty acid oxidation in M2 macrophages. Ultimately, targeting lipid metabolism in macrophages can improve the outcome of metabolic diseases. Here, we review the main aspects of macrophage immunometabolism from the perspective of the metabolism of lipids. Building a reliable metabolic network during macrophage activation will bring us closer to targeting macrophages for improving human health.

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“…Besides LPS and leptin, other factors that are elevated in the obese condition, such as saturated fatty acids and glucose, have been discussed as capable of polarizing macrophages towards an inflammatory phenotype but will not be discussed in this review. Instead, the reader is directed to several comprehensive reviews on this topic [38,76,[119][120][121][122][123][124][125][126].…”

Section: Pancreatic Stromal Macrophages In the Obese Statementioning

confidence: 99%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

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Metabolic influence on macrophage polarization and pathogenesis

Cited by 149 publications

References 142 publications

Monitoring Glycolysis and Respiration Highlights Metabolic Inflexibility of Cryptococcus neoformans

Monitoring Glycolysis and Respiration Highlights Metabolic Inflexibility of Cryptococcus neoformans

New Insights on the Role of Lipid Metabolism in the Metabolic Reprogramming of Macrophages

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

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