Single‐Cell Immune Profiling Suggests Non‐Classical Monocyte Is Associated Immunodepression in Tuberculosis Treatment Non‐Responders

Sputum culture conversion (SCC) at 2 months is an early indicator of tuberculosis (TB) treatment response, yet the associated immune alterations remain incompletely defined. We performed single-cell RNA sequencing on peripheral blood mononuclear cells from eight TB patients, stratified by 2-month SCC status. Non-responders showed a relative enrichment of non-classical monocytes and higher TB progression risk scores. CellChat analysis inferred altered IL16 and TRAIL communication involving these cells. CD4+ Tregs in non-responders showed higher LGALS9 expression and inferred GALECTIN signalling towards cytotoxic lymphocyte subsets; cell-level LGALS9 co-expression correlated with HAVCR2 and TIGIT in non-responders. Mature NK subclusters showed distinct enrichment profiles. These results describe an observational, transcriptomic and computationally inferred immune network associated with early treatment non-response. They generate candidate biomarkers and hypotheses for prospective protein-level and functional validation.