ArticleBMC immunology2025
Single-cell transcriptomics of cervical lymph node tuberculosis reveals cellular heterogeneity and enhanced cellular communication.
Article in BMC immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveDespite advances in understanding systemic immune responses to Mycobacterium tuberculosis (Mtb), the localized immune dynamics within infected lymph nodes, particularly cell-type-specific transcriptional reprogramming and intercellular crosstalk, remain poorly defined, impeding targeted therapy development. By means of single-cell transcriptomics, the objective was to dissect the immune microenvironment and map intercellular crosstalk in Mtb-infected cervical lymph nodes, with the purpose of uncovering the mechanisms of localized immunity and immunopathology.
methodsPaired Mtb-positive cervical swollen lymph nodes (SLN) and adjacent Mtb-negative normal-appearing lymph nodes (NLN) from five cervical LNTB patients were analyzed using single-cell RNA sequencing (scRNA-seq). Computational network modeling (CellChat) and flow cytometry validation were employed to map immune cell heterogeneity and cell–cell communication.
resultsScRNA-seq identified ten T cell subsets, ten B cell subsets, and six myeloid subsets, revealing conserved frequencies but substantial transcriptional reprogramming in SLN. The SLN exhibited extensive upregulation of pro-inflammatory pathways across T, B, and myeloid cells, accompanied by minimal alterations in subset frequencies. IL1B + macrophages in SLN showed an enrichment of genes associated with oxidative phosphorylation, antigen presentation, and inflammasome-related genes. The SLN demonstrated an increased cell–cell communication driven by the crosstalk between macrophage and CD8 + T/NKT cells. Validation through flow cytometry confirmed comparable proportions of immune subsets between the SLN and the NLN, which was consistent with the findings of scRNA-seq.
conclusionsThis study delineates a spatially coordinated immune strategy in cervical LNTB. In this context, Mtb infection induces transcriptional and metabolic reprogramming rather than subset redistribution. The strengthened interaction between macrophages and T cells emphasizes that cellular immunity serves as the main impetus for bacterial containment. Nevertheless, there are trade-offs between inflammation and tissue integrity. These insights provide a framework for developing therapies that target intercellular networks to achieve a balance between immunity and pathology in LNTB.
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