Spatiotemporal proteomic profiling of the pro-inflammatory response to lipopolysaccharide in the THP-1 human leukaemia cell line

Claire M. Mulvey, Lisa M. Breckels, Oliver M. Crook, David J. Sanders, Andre L. R. Ribeiro, Aikaterini Geladaki, Andy Christoforou, Nina Kočevar Britovšek, Tracey Hurrell, Michael J. Deery, Laurent Gatto, Andrew M. Smith () and Kathryn S. Lilley ()
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Claire M. Mulvey: University of Cambridge
Lisa M. Breckels: University of Cambridge
Oliver M. Crook: University of Cambridge
David J. Sanders: Eastman Dental Institute, University College London
Andre L. R. Ribeiro: Eastman Dental Institute, University College London
Aikaterini Geladaki: University of Cambridge
Andy Christoforou: Bristol Myers Squibb
Nina Kočevar Britovšek: University of Cambridge
Tracey Hurrell: University of Cambridge
Michael J. Deery: University of Cambridge
Laurent Gatto: University of Cambridge
Andrew M. Smith: Eastman Dental Institute, University College London
Kathryn S. Lilley: University of Cambridge

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Protein localisation and translocation between intracellular compartments underlie almost all physiological processes. The hyperLOPIT proteomics platform combines mass spectrometry with state-of-the-art machine learning to map the subcellular location of thousands of proteins simultaneously. We combine global proteome analysis with hyperLOPIT in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during a lipopolysaccharide (LPS)-induced inflammatory response. We report a highly dynamic proteome in terms of both protein abundance and subcellular localisation, with alterations in the interferon response, endo-lysosomal system, plasma membrane reorganisation and cell migration. Proteins not previously associated with an LPS response were found to relocalise upon stimulation, the functional consequences of which are still unclear. By quantifying proteome-wide uncertainty through Bayesian modelling, a necessary role for protein relocalisation and the importance of taking a holistic overview of the LPS-driven immune response has been revealed. The data are showcased as an interactive application freely available for the scientific community.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26000-9

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DOI: 10.1038/s41467-021-26000-9

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