Cholesterol metabolism: a new molecular switch to control inflammation

Abstract

The immune system protects the body against harm by inducing inflammation. During the immune response, cells of the immune system get activated, divided and differentiated in order to eliminate the danger signal. This process relies on the metabolic reprogramming of both catabolic and anabolic pathways not only to produce energy in the form of ATP but also to generate metabolites that exert key functions in controlling the response. Equally important to mounting an appropriate effector response is the process of immune resolution, as uncontrolled inflammation is implicated in the pathogenesis of many human diseases, including allergy, chronic inflammation and cancer. In this review, we aim to introduce the reader to the field of cholesterol immunometabolism and discuss how both metabolites arising from the pathway and cholesterol homeostasis are able to impact innate and adaptive immune cells, staging cholesterol homeostasis at the centre of an adequate immune response. We also review evidence that demonstrates the clear impact that cholesterol metabolism has in both the induction and the resolution of the inflammatory response. Finally, we propose that emerging data in this field not only increase our understanding of immunometabolism but also provide new tools for monitoring and intervening in human diseases, where controlling and/or modifying inflammation is desirable.

Endosomal Cholesterol in Viral Infections – A Common Denominator?

“…As pointed out earlier, cholesterol has the potential to control innate immunity with respect to IFN responses. Additionally, there is growing awareness that its anabolism and its derivatization into oxysterols or BAs mediate central aspects of inflammation ( Spann et al, 2012 ; Perucha et al, 2019 ; Willinger, 2019 ; Cardoso and Perucha, 2021 ). How and if cholesterol trafficking to these organelles affects these mechanisms remains largely elusive so far.…”

Clinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques

“…In affected animals, AEs were preceded by an elevation of inflammatory markers including NLR ratio, CRP, MCP-1, IL-6 with hypoalbuminemia and hypocholesterolemia related to the high-energy demand in cachexia-associated systemic inflammation. [95][96][97][98] These markers were strongly correlated with the severity of AEs. This chronic, systemic inflammation-mediated catabolism worsened with increasing time posttransplant, was associated with increased expression of CRP and CD40 in livers and kidneys of xenoislet but not alloislet recipients, and appeared unresponsive to maintenance immunosuppression with CTLA4Ig, tacrolimus, and rapamycin.…”

Comparative Transcriptome Analysis of Organ-Specific Adaptive Responses to Hypoxia Provides Insights to Human Diseases

“…In recent years, the roles of cholesterol in the immune system have been discussed. Cardoso et al indicated that the level of cholesterol could respond to immune responses (including innate and adaptive immune cell systems) [ 45 ]. Intriguingly, a gene of C. burnetii encoding a sterol-modifying enzyme was determined to be critical for the survival in phagolysosome-like vacuoles and essential for pathogenesis [ 46 ].…”