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Holistic Characterization of a Salmonella Typhimurium Infection Model Using Integrated Molecular Imaging
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- Strittmatter, Nicole (författare)
- AstraZeneca, Clin Pharmacol & Safety Sci, R&D, Cambridge CB4 0WG, England.;Tech Univ Munich, Fac Chem, D-85748 Garching, Germany.
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- Kanvatirth, Panchali (författare)
- Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.;AstraZeneca, R&D Biopharmaceut, Discovery Sci, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
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- Inglese, Paolo (författare)
- Imperial Coll London, Fac Med, Dept Metab Digest & Reprod, London SW7 2AZ, England.
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- AstraZeneca, Clin Pharmacol & Safety Sci, R&D, Cambridge CB4 0WG, England;Tech Univ Munich, Fac Chem, D-85748 Garching, Germany. Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.;AstraZeneca, R&D Biopharmaceut, Discovery Sci, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England. (creator_code:org_t)
- 2021-11-12
- 2021
- Engelska.
- Ingår i: Journal of the American Society for Mass Spectrometry. - : American Chemical Society (ACS). - 1044-0305 .- 1879-1123. ; 32:12, s. 2791-2802
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- mass spectrometry imaging
- imaging mass cytometry
- Salmonella infection
- network analysis
- multimodal data integration
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