Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli

Rattigan, K. M., Pountain, A. W. , Regnault, C., Achcar, F. , Vincent, I. M. , Goodyear, C. S. and Barrett, M. P. (2018) Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli. PLoS ONE, 13(3), e0194126. (doi: 10.1371/journal.pone.0194126) (PMID:29538444) (PMCID:PMC5851634)

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Abstract

Priming and activating immune stimuli have profound effects on macrophages, however, studies generally evaluate stimuli in isolation rather than in combination. In this study we have investigated the effects of pro-inflammatory and anti-inflammatory stimuli either alone or in combination on macrophage metabolism. These stimuli include host factors such as IFNγ and ovalbumin-immunoglobulin immune complexes, or pathogen factors such as LPS. Untargeted LC-MS based metabolomics provided an in-depth profile of the macrophage metabolome, and revealed specific changes in metabolite abundance upon either individual stimuli or combined stimuli. Here, by factoring in an interaction term in the linear model, we define the metabolome interactome. This approach allowed us to determine whether stimuli interact in a synergistic or antagonistic manner. In conclusion this study demonstrates a robust approach to interrogate immune-metabolism, especially systems that model host-pathogen interactions.

Item Type:Articles
Keywords:biology and life sciences, medicine and health sciences, physical sciences.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rattigan, Dr Kevin and Vincent, Dr Isabel and Regnault, Mr Clement and Achcar, Dr Fiona and Goodyear, Professor Carl and Pountain, Andrew and Barrett, Professor Michael
Creator Roles:
Rattigan, K. M.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review and editing
Pountain, A. W.Formal analysis, Methodology
Regnault, C.Methodology
Achcar, F.Formal analysis, Methodology
Vincent, I. M.Formal analysis
Goodyear, C. S.Conceptualization, Funding acquisition, Investigation, Methodology, Supervision, Writing – review and editing
Barrett, M. P.Conceptualization, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing – original draft, Writing – review and editing
Authors: Rattigan, K. M., Pountain, A. W., Regnault, C., Achcar, F., Vincent, I. M., Goodyear, C. S., and Barrett, M. P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2018 Rattigan et al.
First Published:First published in PLoS ONE 1393):e0194126
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
690321Gene expression in Plasmodium parasites: the molecular mechanics of gametocytogenesis (and variant transcription of genes)Andrew WatersWellcome Trust (WELLCOTR)107046/Z/15/ZIII - PARASITOLOGY
699651Metabolic subversion in the interaction between leishmania and the macrophageFiona AchcarLeverhulme Trust (LEVERHUL)ECF-2015-392RI INFECTION IMMUNITY & INFLAMMATION