Holistic Characterization of a Salmonella Typhimurium Infection Model Using Integrated Molecular Imaging.

Autor:	Strittmatter N; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Kanvatirth P; Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, U.K., Inglese P; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, U.K., Race AM; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Nilsson A; Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, 751 24 Uppsala, Sweden.; Science for Life Laboratory, Spatial Mass Spectrometry, Uppsala University, 751 24 Uppsala, Sweden., Dannhorn A; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Kudo H; Division of Digestive Diseases, Section of Pathology, Imperial College London, St. Mary's Hospital, London W2 1NY, U.K., Goldin RD; Division of Digestive Diseases, Section of Pathology, Imperial College London, St. Mary's Hospital, London W2 1NY, U.K.; Department of Cellular Pathology, Charing Cross Hospital, London W6 8RF, U.K., Ling S; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Wong E; Biologics Engineering, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Seeliger F; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Serra MP; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Hoffmann S; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.; BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, U.K., Maglennon G; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Hamm G; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Atkinson J; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Jones S; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K., Bunch J; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, U.K.; National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory, Teddington TW11 0LW, U.K., Andrén PE; Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, 751 24 Uppsala, Sweden.; Science for Life Laboratory, Spatial Mass Spectrometry, Uppsala University, 751 24 Uppsala, Sweden., Takats Z; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, U.K., Goodwin RJA; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, U.K., Mastroeni P; Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, U.K.
Jazyk:	angličtina
Zdroj:	Journal of the American Society for Mass Spectrometry [J Am Soc Mass Spectrom] 2021 Dec 01; Vol. 32 (12), pp. 2791-2802. Date of Electronic Publication: 2021 Nov 12.
DOI:	10.1021/jasms.1c00240
Abstrakt:	A more complete and holistic view on host-microbe interactions is needed to understand the physiological and cellular barriers that affect the efficacy of drug treatments and allow the discovery and development of new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry imaging (MSI) and same section imaging mass cytometry (IMC) to study the effects of Salmonella Typhimurium infection in the liver of a mouse model using the S. Typhimurium strains SL3261 and SL1344. This approach enables correlation of tissue morphology and specific cell phenotypes with molecular images of tissue metabolism. IMC revealed a marked increase in immune cell markers and localization in immune aggregates in infected tissues. A correlative computational method (network analysis) was deployed to find metabolic features associated with infection and revealed metabolic clusters of acetyl carnitines, as well as phosphatidylcholine and phosphatidylethanolamine plasmalogen species, which could be associated with pro-inflammatory immune cell types. By developing an IMC marker for the detection of Salmonella LPS, we were further able to identify and characterize those cell types which contained S. Typhimurium.
Databáze:	MEDLINE
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