Metabolic Control of Smoldering Neuroinflammation.

Luca Peruzzotti-Jametti,Cory M Willis,Regan Hamel,Grzegorz Krzak,Stefano Pluchino

doi:10.3389/fimmu.2021.705920

Luca Peruzzotti-Jametti, Cory M Willis + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2021.705920

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Abstract

Compelling evidence exists that patients with chronic neurological conditions, which includes progressive multiple sclerosis, display pathological changes in neural metabolism and mitochondrial function. However, it is unknown if a similar degree of metabolic dysfunction occurs also in non-neural cells in the central nervous system. Specifically, it remains to be clarified (i) the full extent of metabolic changes in tissue-resident microglia and infiltrating macrophages after prolonged neuroinflammation (e.g., at the level of chronic active lesions), and (ii) whether these alterations underlie a unique pathogenic phenotype that is amenable for therapeutic targeting. Herein, we discuss how cell metabolism and mitochondrial function govern the function of chronic active microglia and macrophages brain infiltrates and identify new metabolic targets for therapeutic approaches aimed at reducing smoldering neuroinflammation.

Highlights

Cellular metabolism is at the foundation of all biological activities [1]
In FABP5 knock out bone marrow-derived macrophages (BMDMs), stimulation with inflammatory (LPS and IFN-g) or anti-inflammatory (IL-4) mediators results in significantly higher expression of anti-inflammatory factors [105, 108]. These findings suggest that loss of FABP5 function promotes anti-inflammatory responses in macrophages
The growing interest in immunometabolism has demonstrated that myeloid cells are well-equipped to quickly adapt to varying environmental challenges, even when access to carbon sources is highly variable, such as in conditions of inflammation

Summary

Introduction

Cellular metabolism is at the foundation of all biological activities [1]. While the metabolic processes that support cellular bioenergetics and survival have been extensively studied [2, 3], the role of metabolism in guiding complex cellular functions is yet to be completely understood. BV2 microglia, and the B6M7 microglial cell line, treated with LPS and IFN-g exhibit the expected metabolic shift towards enhanced glycolysis and increased gene expression of GLUT1.

Results

Conclusion