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Spatially Resolved Immunometabolism to Understand Infectious Disease Progression

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Publication details

JournalFrontiers in Microbiology
DateAccepted/In press - 30 Jul 2021
DatePublished (current) - 19 Aug 2021
Volume12
Number of pages9
Original languageEnglish

Abstract

Infectious diseases, including those of viral, bacterial, fungal, and parasitic origin are often characterized by focal inflammation occurring in one or more distinct tissues. Tissue-specific outcomes of infection are also evident in many infectious diseases, suggesting that the local microenvironment may instruct complex and diverse innate and adaptive cellular responses resulting in locally distinct molecular signatures. In turn, these molecular signatures may both drive and be responsive to local metabolic changes in immune as well as non-immune cells, ultimately shaping the outcome of infection. Given the spatial complexity of immune and inflammatory responses during infection, it is evident that understanding the spatial organization of transcripts, proteins, lipids, and metabolites is pivotal to delineating the underlying regulation of local immunity. Molecular imaging techniques like mass spectrometry imaging and spatially resolved, highly multiplexed immunohistochemistry and transcriptomics can define detailed metabolic signatures at the microenvironmental level. Moreover, a successful complementation of these two imaging techniques would allow multi-omics analyses of inflammatory microenvironments to facilitate understanding of disease pathogenesis and identify novel targets for therapeutic intervention. Here, we describe strategies for downstream data analysis of spatially resolved multi-omics data and, using leishmaniasis as an exemplar, describe how such analysis can be applied in a disease-specific context.

Bibliographical note

Funding Information:
Funding. This work was funded by the York-Maastricht Partnership program and supported by a Wellcome Trust Senior Investigator Award to PMK (WT106203). This research was part of the M4I research program and received financial support from the Dutch Province of Limburg under the LINK program. The figures in this article have been created/modified using Biorender.

Publisher Copyright:
© Copyright © 2021 Tans, Dey, Dey, Calder, O’Toole, Kaye and Heeren.

    Research areas

  • granulomas, immunometabolism, infectious disease, inflammation, leishmaniasis, mass spectrometry imaging, multi-omics, spatial transcriptomics

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