Spatially Resolved Immunometabolism to Understand Infectious Disease Progression

R. Tans, S. Dey, N.S. Dey, G. Calder, P. O'Toole, P.M. Kaye*, R.M.A. Heeren*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Web of Science)

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.
Original languageEnglish
Article number709728
Number of pages9
JournalFrontiers in microbiology
Volume12
DOIs
Publication statusPublished - 19 Aug 2021

Keywords

  • immunometabolism
  • infectious disease
  • inflammation
  • granulomas
  • mass spectrometry imaging
  • spatial transcriptomics
  • multi-omics
  • leishmaniasis
  • IMAGING MASS-SPECTROMETRY
  • DUAL RNA-SEQ
  • INFLAMMATION
  • MACROPHAGES
  • RESOLUTION
  • NETWORK
  • HETEROGENEITY
  • DYSFUNCTION
  • EXPRESSION
  • IL-1-BETA

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