Unveiling the immunological landscape of disseminated tuberculosis: a single-cell transcriptome perspective

Area of Science:

• Immunology
• Tuberculosis Research
• Single-cell Genomics

Background:

• Hematogenous disseminated tuberculosis (DTB) pathogenesis remains unclear.
• Understanding DTB's immunological characteristics is vital for disease elucidation.

Purpose of the Study:

• To investigate the immunological landscape of DTB using single-cell RNA and TCR sequencing.
• To identify key cellular and molecular features associated with DTB.

Main Methods:

• Single-cell RNA and T cell receptor (TCR) sequencing performed on DTB patient samples.
• Integrated analysis with published data from latent TB, active TB, and healthy controls.

Main Results:

• DTB patients exhibited higher inflammatory cells (monocytes, macrophages) and lower lymphocytes, indicating lymphopenia.
• T cell pseudotime analysis revealed functional exhaustion, with reduced hypervariable gene expression.
• A significant absence of mucosal-associated invariant T (MAIT) cells and unique TCR polymorphisms/clonotypes were observed in DTB patients.
• Reduced "CAAMD" motif in complementarity determining region 3 (CDR3) was a key finding.

Conclusions:

• Lymphopenia, T cell exhaustion, and distinct TCR signatures are implicated in DTB pathogenesis.
• Altered TCR clonotypes and reduced "CAAMD" motif provide novel insights for targeted immunological interventions in DTB.