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Objective <p>Despite advances in understanding systemic immune responses to <i>Mycobacterium tuberculosis</i> (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.</p> Methods <p>Paired 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.</p> Results <p>ScRNA-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&#xa0;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.</p> Conclusions <p>This 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.</p>

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Single-cell transcriptomics of cervical lymph node tuberculosis reveals cellular heterogeneity and enhanced cellular communication

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月21日

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  • Guohui Xiao,
  • Haijiang Wang,
  • Su Zhang,
  • Xuefeng Zhou,
  • Min Ou,
  • Xiangmei Zhang,
  • Guobao Li,
  • Aimei Liu,
  • Shimin Shuai,
  • Guoliang Zhang

摘要

Objective

Despite 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.

Methods

Paired 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.

Results

ScRNA-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.

Conclusions

This 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.