The 3D landscape of infection: spatial organization and in vitro models

Microbial infections rarely consist of free-floating cells. Instead, pathogens and immune cells are typically organized into complex three-dimensional (3D) structures, including biofilms, abscesses, and granulomas, which can serve to constrain pathogen dissemination. At the same time, these architectures create protective microenvironments that promote microbial persistence, immune evasion, and increased resistance to antimicrobial therapies. A mechanistic understanding of how spatially organized tissue structures and local microenvironmental cues shape host-pathogen dynamics may open new avenues for therapeutic interventions, for example by improving targeted drug delivery, enhancing antibiotic penetration, or disrupting protective microbial niches. In this review, we summarize emerging insights into the 3D landscape of infections and highlight advances in experimental platforms that more faithfully recapitulate tissue architecture, including 3D cell culture systems, bioprinted tissue, organoids, and organ-on-chip technologies. Finally, we discuss how integrating spatial parameters into infection models reshapes our understanding of pathogenesis and opens new conceptual and therapeutic avenues for combating infections.