A single-cell atlas of peripheral immunity suggests immune subset attrition during tuberculosis dissemination.

ObjectiveThis study investigated immune lineage remodeling and intercellular communication to elucidate the mechanisms driving the progression from active tuberculosis to disseminated tuberculosis.MethodsWe integrated single-cell RNA-sequencing datasets of peripheral blood mononuclear cells from healthy controls, patients with active tuberculosis, and patients with disseminated tuberculosis (n = 3 for each group) to perform cellular clustering, functional assessment, and communication network analyses.ResultsAnalysis identified 16 clusters across 5 major lineages. Although global cellular proportions remained statistically stable across patient cohorts, disease progression was characterized by distinct cell-intrinsic transcriptomic shifts and subset-specific remodeling. This landscape was highlighted by the systematic peripheral depletion of homeostatic "guardian" monocytes, alongside functional disruptions in natural killer and B-cell states, and a severe-stage-specific accumulation of exhausted T cells. Consequently, circulating intercellular communication networks were broadly attenuated in infected groups, featuring diminished receptor-ligand interactions between peripheral dendritic cells and naïve CD8