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Review | Open Access

Cytomics-driven insights for investigating host–pathogen interactions

Andrea Cossarizza1,2( )Cristina Mussini3Diana Boraschi4Aldo Tagliabue4
Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia School of Medicine, Modena, Emilia-Romagna, Italy
National Institute for Cardiovascular Research, Emilia-Romagna, Italy
Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia School of Medicine, Modena, Emilia-Romagna, Italy
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong, China
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Highlights

• 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, and improves vaccine and epidemic strategies.

Abstract

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, as well as 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.

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hLife
Pages 399-422

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Cite this article:
Cossarizza A, Mussini C, Boraschi D, et al. Cytomics-driven insights for investigating host–pathogen interactions. hLife, 2026, 4(7): 399-422. https://doi.org/10.1016/j.hlife.2026.04.003

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Received: 16 February 2026
Revised: 10 April 2026
Accepted: 24 April 2026
Published: 01 July 2026
© 2026 The Author(s).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).