Advances in Spatial Transcriptomics for Infectious Disease Research: Insight for Vaccine Development

Area of Science:

• Infectious disease research
• Molecular biology
• Genomics

Background:

• Spatial transcriptomics (ST) integrates gene expression data with tissue architecture, bridging bulk, single-cell, and histological analyses.
• ST has rapidly evolved since 2016, transforming infectious disease research by enabling direct mapping of host-pathogen interactions within intact tissues.

Purpose of the Study:

• To review the application and impact of spatial transcriptomics in infectious disease research.
• To highlight how ST elucidates spatially organized immune responses, tissue remodeling, and pathogen niches.

Main Methods:

• Overview of current ST platforms: sequencing-based (Visium, GeoMx, Stereo-seq) for whole-transcriptome coverage and imaging-based (Xenium, CosMx, MERFISH) for targeted gene panels.
• Analysis of ST applications in viral (e.g., COVID-19), bacterial (e.g., tuberculosis, Shigella), and parasitic (e.g., malaria) infections.

Main Results:

• ST reveals heterogeneity in infection microenvironments, spatial immune activation, and pathogen niches.
• Studies show ST delineating granuloma architecture, mapping vaccine responses, and identifying localized inflammatory hotspots.
• ST uncovered microenvironmental control of T-cell differentiation in malaria and variant-specific inflammatory patterns in viral infections.

Conclusions:

• Spatial transcriptomics provides powerful insights into host-pathogen interactions and immune dynamics within tissues.
• Despite limitations like RNA quality and cost, ST is crucial for understanding infectious diseases and informing vaccine design.
• ST is becoming a standard tool in infectious disease biology, aiding in the identification of tissue-specific immune programs and protective microenvironments.