Cytomics, the high-dimensional profiling of immune cells, provides a systems-level view of host responses to infection. Unlike traditional diagnostics focused on pathogen detection or early immune activation, cytomics captures rare and functionally specialized immune subsets linked to disease severity and clinical outcome. In this review, we explore how advances in spectral cytometry, mass cytometry, and multimodal single-cell platforms enable unprecedented resolution of immune complexity during infection by summarizing cytomics evolution, high dimensional single-cell and multimodal technologies, and their roles in defining immune heterogeneity and host–pathogen interactions across infectious diseases. Several single-cell technologies rely on antibodies conjugated to fluorochromes or non-radioactive isotopes, generating high-dimensional datasets processed with advanced computational tools, enabling unprecedented precision in defining cell populations and supporting diagnostic advances. During infections, cytomic approaches map immune architecture, identify dysfunctional or protective cell states, and monitor therapeutic responses. In viral infections, it detects hyperinflammatory monocytes and exhausted T-cell subsets; in bacterial diseases, it reveals immunosuppressive monocytes and disrupted neutrophil networks; in parasitic infections, it clarifies mechanisms of persistence and clearance. Integrated with complementary omics technologies, cytomics informs personalized immunomodulatory strategies and rational vaccine design. This review provides a unified framework for applying cytomics to precision diagnostics, therapeutic decision-making, vaccine development, and population-level preparedness, positioning high-dimensional immune profiling as a cornerstone of modern infectious-disease management. • Cytomics profiles immune cells during infections, revealing complex host responses and rare cells. • Immune signatures linked to severity in viruses and dysfunctions in bacterial disease are detected. • Pathogen persistence or clearance and immune changes are shown in malaria and leishmaniasis. • Cytomics enables immune monitoring, personalized therapies, improves vaccine and epidemic strategies.
Cossarizza et al. (Fri,) studied this question.