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.
Highlights
Immuno-metabolism is a rapidly growing area of research
In both experiments, using different types of inflammatory or anti-inflammatory macrophage, clear separation was evident when the data was subjected to principal component analysis (PCA) with the inflammatory macrophages being the most distinct (Fig 1D and 1E)
This study has revealed hitherto unexpected complexity in macrophage response to different immune-stimuli
Summary
Immuno-metabolism is a rapidly growing area of research. Recent studies have shown how metabolites such as succinate and itaconate modulate the function of key innate immune cells such as macrophages [1,2,3,4]. The exposure of macrophages to various stimuli such as cytokines or pathogenic antigens results in the initiation of various signalling cascades through their specific receptors (i.e., cytokine receptors or pattern recognition receptors (PRRs)). Metabolomic profiling of polarised macrophage determines the discrete metabolomic signature and interactome and this funding covered stipend, bench fees. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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