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Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
Published on: November 28, 2015
Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization
Ekaterina A Gorshkova1,2,3, Ekaterina O Gubernatorova1,3, Ekaterina M Dvorianinova1
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Abstract:
The naked mole-rat (NMR) is a unique long-lived rodent which is highly resistant to age-associated disorders and cancer. The immune system of NMR possesses a distinct cellular composition with the prevalence of myeloid cells. Thus, the detailed phenotypical and functional assessment of NMR myeloid cell compartment may uncover novel mechanisms of immunoregulation and healthy aging. In this study gene expression signatures, reactive nitrogen species and cytokine production, as well as metabolic activity of classically (M1) and alternatively (M2) activated NMR bone marrow-derived macrophages (BMDM) were examined. Polarization of NMR macrophages under pro-inflammatory conditions led to expected M1 phenotype characterized by increased pro-inflammatory gene expression, cytokine production and aerobic glycolysis, but paralleled by reduced production of nitric oxide (NO). Under systemic LPS-induced inflammatory conditions NO production also was not detected in NMR blood monocytes. Altogether, our results indicate that NMR macrophages are capable of transcriptional and metabolic reprogramming under polarizing stimuli, however, NMR M1 possesses species-specific signatures as compared to murine M1, implicating distinct adaptations in NMR immune system.
Insights
Naked mole-rats exhibit unique immune cell functions, with their macrophages reprogramming effectively but showing distinct M1 signatures compared to mice. This suggests novel adaptations for healthy aging and disease resistance.
Area of Science:
- Immunology
- Comparative Biology
- Aging Research
Background:
- Naked mole-rats (NMR) are exceptionally long-lived rodents resistant to cancer and aging.
- NMR possess a unique myeloid cell-dominant immune system.
- Understanding NMR immune mechanisms may reveal insights into healthy aging and immunoregulation.
Purpose of the Study:
- To investigate the phenotypical and functional characteristics of NMR myeloid cells.
- To analyze gene expression, reactive nitrogen species, and cytokine production in NMR macrophages.
- To assess metabolic activity and reprogramming capabilities of NMR macrophages.
Main Methods:
- Bone marrow-derived macrophages (BMDM) from NMR were polarized into classically (M1) and alternatively (M2) activated states.
- Gene expression signatures were analyzed.
- Nitric oxide (NO) and cytokine production were measured.
- Metabolic activity, including aerobic glycolysis, was assessed.
Main Results:
- NMR macrophages demonstrated transcriptional and metabolic reprogramming upon polarization.
- M1 polarization increased pro-inflammatory gene expression and cytokine production, alongside enhanced aerobic glycolysis.
- A notable finding was the reduced production of nitric oxide (NO) in M1-polarized NMR macrophages and blood monocytes.
- NMR M1 macrophages displayed species-specific gene expression signatures compared to murine M1 macrophages.
Conclusions:
- NMR macrophages are capable of significant reprogramming in response to stimuli.
- The reduced NO production in M1 macrophages represents a species-specific adaptation.
- These findings highlight distinct immune system adaptations in naked mole-rats, potentially contributing to their longevity and disease resistance.
