Immune oxysterols: Role in mycobacterial infection and inflammation
File(s)
Published version
OA Location
Author(s)
Bah, SY
Dickinson, P
Forster, T
Kampmann, B
Ghazal, P
Type
Journal Article
Abstract
Infection remains an important cause of morbidity and mortality. Natural defenses to infection are mediated by intrinsic/innate and adaptive immune responses. While our understanding is considerable it is incomplete and emerging areas of research such as those related to the immune-metabolic axis are only beginning to be appreciated. There is increasing evidence showing a connection between immune signalling and the regulation of sterol and fatty acid metabolism. In particular, metabolic intermediates of cholesterol biosynthesis and its oxidized metabolites (oxysterols) have been shown to regulate adaptive immunity and inflammation and for innate immune signalling to regulate the dynamics of cholesterol synthesis and homeostasis. The side-chain oxidized oxysterols, 25-hydroxycholesterol (25HC) and vitamin D metabolites (vitamin D3 and vitamin D2), are now known to impart physiologically profound effects on immune responses. Macrophages play a frontline role in this process connecting immunity, infection and lipid biology, and collaterally are a central target for infection by a wide range of pathogens including viruses and bacteria, especially intracellular bacteria such as mycobacteria. Clinical manifestations of disease severity in the infected host are likely to pay tribute to perturbations of the metabolic-immune phenomena found in lymphocytes and myeloid cells. Historically and consistent with this notion, vitamin D based oxysterols have had a long association with promoting clinical improvements to patients infected with Mycobacterium tuberculosis. Hence understanding the role of early metabolic mediators of inflammatory responses to infection in particular oxysterols, will aid in the development of urgently needed host directed therapeutic and diagnostic design innovation to combat adverse infection outcomes and antibiotic resistance.
Date Issued
2016-05-04
Date Acceptance
2016-04-25
Citation
Journal of Steroid Biochemistry and Molecular Biology, 2016, 169, pp.152-163
ISSN
1879-1220
Publisher
Elsevier
Start Page
152
End Page
163
Journal / Book Title
Journal of Steroid Biochemistry and Molecular Biology
Volume
169
Copyright Statement
© 2016 The Authors. Published by Elsevier Ltd. This is an open access article under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Sponsor
National Institute for Health Research
Identifier
PII: S0960-0760(16)30111-X
Grant Number
SRF-2009-02-07
Subjects
25 hydroxycholesterol
Cholesterol
Immunity
Infection
Oxysterols
Tuberculosis
Vitamin D
Publication Status
Published