Spatially Resolved Immunometabolism to Understand Infectious Disease Progression

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.

Tissue Specific Dual RNA-Seq Defines Host–Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum

“…Due to its capability to metabolize oxidized fatty acids and generate lipoxin and resolvins as well, it can also contribute to counteract inflammation ( 30 , 31 ). Since RNA-seq studies cannot give a picture of the relative amounts of lipid mediators in the tissue to allow predictions on the degree of inflammation, metabolomic studies would be more appropriate to address such potential differences ( 32 ). Among the unique host DE genes for each parasite species, some were related to the immune response.…”

Tissue specific dual RNA-seq defines host-parasite interplay in murine visceral leishmaniasis caused by Leishmania donovani and Leishmania infantum

“…Due to its capability to metabolize oxidised fatty acids and generate lipoxin and resolvins as well, it can also contribute to counteract inflammation (28, 29). Since RNA-seq studies cannot give a picture of the relative amounts of lipid mediators in the tissue to allow predictions on the degree of inflammation, metabolomic studies would be more appropriate to address such potential differences (30). Among the unique host DE genes for each parasite species, some were related to the immune response.…”

From structural determination of natural products in complex mixtures to single cell resolution: Perspectives on advances and challenges for mass spectrometry

“…The technological advancement, in terms of equipment, is already available, and recent publications allow us to dream with this new resolution to the chemistry of natural products. In a recent article, Tans and coworkers use spatial metabolomics where an image and MS/MS data are simultaneously generated, leading to the possibility of annotating the substances present in regions of 5 μm (Tans R. et al, 2021), something never thought of before. The addition of a third dimension provided by ionic mobility in imaging systems opens up enormous potential for the same studies in single-cell analysis.…”