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

• Published in: Nature communications Vol. 12; no. 1; p. 5773
• Main Authors: Mulvey, Claire M., Breckels, Lisa M., Crook, Oliver M., Sanders, David J., Ribeiro, Andre L. R., Geladaki, Aikaterini, Christoforou, Andy, Britovšek, Nina Kočevar, Hurrell, Tracey, Deery, Michael J., Gatto, Laurent, Smith, Andrew M., Lilley, Kathryn S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 14; 631/114/2784; 631/1647/2067; 631/250/2504/342/1726; 631/45/475; 82/51; 82/58; Algorithms; Anti-Infective Agents - metabolism; Anti-Inflammatory Agents - metabolism; Antigen Presentation; Autophagosomes - metabolism; Bayes Theorem; Bayesian analysis; Cell Cycle Checkpoints; Cell Membrane - metabolism; Cell migration; Cell Nucleus - metabolism; Cell Shape; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunity; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammatory response; Innate immunity; Interferon; Learning algorithms; Leukemia; Leukemia - immunology; Leukemia - metabolism; Leukemia - pathology; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Localization; Lymphocyte Activation - immunology; Lysosomes - metabolism; Machine learning; Mass spectrometry; Mass spectroscopy; multidisciplinary; Neoplasm Proteins - metabolism; Protein Transport; Proteins; Proteome - metabolism; Proteomes; Proteomics; rho GTP-Binding Proteins - metabolism; Science; Science (multidisciplinary); Signal Transduction; T-Lymphocytes - immunology; THP-1 Cells; Time Factors; Translocation; Transport Vesicles - metabolism; Up-Regulation; Workflow
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26000-9

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. “Protein relocalisation plays a major role in the innate immune response but remains incompletely characterised. Here, the authors combine temporal proteomics with LOPIT, a spatial proteomic workflow, in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during the LPS-induced immune response in THP-1 cells.