Peroxisomes in Immune Response and Inflammation.

Francesca Di Cara,Pierre Andreoletti,Margret H Bülow,Gérard Lizard,Mustapha Cherkaoui-Malki,Julia Sellin,Anne Vejux,Doriane Trompier,Stéphane Savary

doi:10.3390/ijms20163877

Abstract

The immune response is essential to protect organisms from infection and an altered self. An organism’s overall metabolic status is now recognized as an important and long-overlooked mediator of immunity and has spurred new explorations of immune-related metabolic abnormalities. Peroxisomes are essential metabolic organelles with a central role in the synthesis and turnover of complex lipids and reactive species. Peroxisomes have recently been identified as pivotal regulators of immune functions and inflammation in the development and during infection, defining a new branch of immunometabolism. This review summarizes the current evidence that has helped to identify peroxisomes as central regulators of immunity and highlights the peroxisomal proteins and metabolites that have acquired relevance in human pathologies for their link to the development of inflammation, neuropathies, aging and cancer. This review then describes how peroxisomes govern immune signaling strategies such as phagocytosis and cytokine production and their relevance in fighting bacterial and viral infections. The mechanisms by which peroxisomes either control the activation of the immune response or trigger cellular metabolic changes that activate and resolve immune responses are also described.

Highlights

Peroxisomes are almost ubiquitous metabolic organelles conserved across the eukaryotes
Another connection of the intersection between peroxisome activity and inflammation originated from the studies reported by Oruqaj et al who demonstrated the implication of peroxisomes in regulating inflammatory signaling in immune cells, and in other tissues such as fibroblasts from human idiopathic pulmonary fibrosis (IPF) [82]
In post-mortem samples of young X-linked adrenoleukodystrophy (X-ALD) patients, adult X-ALD patients, and AMN patients, IL-1 and ICAM-1 were detected in microvessels and astrocytes, while tumor necrosis factor (TNF)-α was observed in macrophages and more significantly in astrocytes [84]

Summary

Introduction

Peroxisomes are almost ubiquitous metabolic organelles conserved across the eukaryotes. The authors suggest that the peroxisomal product necessary to the anti-inflammatory effect in LPS-stimulated macrophages is DHA, a precursor of many lipid resolution mediators (Figure 1), leaving to speculate that peroxisomes produce biolipids to initiate the resolution of inflammation In this process the activity of NF-κB is not affected, suggesting that peroxisomes can regulate the immune cell activation with different strategies that are NF-κB dependent or independent. The plasma levels of cholesterol and its peroxidative products such as 7-ketocholesterol and 7β-hydroxycholesterol were found increased in X-ALD patients, and oxysterols likely participate in age related diseases [80,81] (Figure 1) Another connection of the intersection between peroxisome activity and inflammation originated from the studies reported by Oruqaj et al who demonstrated the implication of peroxisomes in regulating inflammatory signaling in immune cells, and in other tissues such as fibroblasts from human idiopathic pulmonary fibrosis (IPF) [82].

Peroxisome Metabolism Protects from Neuroinflammation

Peroxisome Metabolism during Aging

Peroxisomes Act as Signaling Platforms to Activate Antiviral Responses

Peroxisomal Functions are Linked to Phagocytosis Capacity

Findings

Conclusion and Future Remarks