Paired single-cell and spatial transcriptional profiling reveals a central osteopontin macrophage response mediating tuberculous granuloma formation.

ABSTRACT: Granulomas are classic manifestations of tuberculosis pathogenesis. They result from an ensemble of immune responses to Mycobacterium tuberculosis infection, but the identities, arrangement, cellular interactions, and regulation of the cells that comprise them have thus far been incompletely understood. To better understand the composition of granulomas, we conducted spatial and single-cell RNA sequencing of granulomas in biopsy specimens from patients with tuberculosis. We found that granulomas consist of concentric transcriptional laminae surrounding areas of central necrosis. We identified distinct populations of granuloma-associated stromal cells, fibroblasts, lymphocytes, mast cells, dendritic cells, neutrophils, and macrophages. Furthermore, gene expression among these cell po

SUBMITTER: Pyle CJ 

PROVIDER: S-EPMC12421895 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature