Paired single-cell and spatial transcriptional profiling reveals a central osteopontin macrophage response mediating tuberculous granuloma formation
Mycobacterial granulomas are categorical 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 has thus far been incompletely understood. Using the Mycobacterium marinum-zebrafish model we found that mycobacterial infection induces spp1 expression in macrophages and that spp1 ablation results in granuloma formation defects and reduced survival in adult animals. To determine the impact of mycobacterial infection on the transcriptional response of nascent granuloma macrophages we conducted bulk RNA-seq on flow-sorted infected and uninfected macrophages isolated from infected larvae or uninfected controls. Overall design: To determine the impact of mycobacterial infection on the transcriptional response of nascent granuloma macrophages we conducted bulk RNA-seq on flow-sorted infected and uninfected macrophages isolated from infected larvae or uninfected controls.