Single-cell profiling of physically interacting immune cells using image-guided sorting
Year: 2026
Type: preprint
Abstract: immune interactions, yet distinguishing true physical contacts from artifacts remains challenging. Here, we integrated spectral imaging cell sorting with physical cell deconvolution to separate circulating T cell-monocyte doublets from tuberculosis patients into physically interacting (in-contact) and non-interacting (coincidental) populations. Single-cell sequencing of individual cell partners revealed that physical contact is associated with robust signatures distinct from singlets, including unidirectional monocyte-to-T cell RNA transfer, heightened metabolic activity and T cell cytotoxicity, and a trend toward antigen-specific enrichment. These signatures spanned all T cell and monocyte subpopulations, reflecting a global program of T cell-monocyte engagement. Coincidental doublets displayed intermediate transcriptional profiles between singlet and in-contact states, suggesting the presence of recently disrupted or forming physical pairs. This framework provides high-fidelity deconvolution of cellular interactions, uncovering signatures governing T cell-monocyte communication in human disease.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222791113