Spatial transcriptomics of pediatric tuberculosis lymph nodes reveals a conserved hypoxia_SPP1 niche

A hypoxia-associated, SPP1-enriched macrophage microenvironment recurs across 60 pediatric TB granulomas (ages 4–36 months), spanning non-necrotic and necrotic lesions.

• Why it matters: Pediatric mediastinal lymph node granulomas are hard to study directly, leaving the granuloma microenvironment and its host programs poorly defined for host-directed strategy design.
• What they did: Using spatial transcriptomics on 60 granulomas from four children, the study mapped nine recurrent transcriptional microenvironments and tested hypoxia–SPP1 links with pathway analysis, an adult dataset (Spearman rho=0.65), and multiplex immunofluorescence validation.
• The result: The hypoxia–SPP1 association is linked to regions enriched for both M1- and M2-like macrophage programs and antimicrobial plus regulatory pathways, suggesting partial immune control and a potential niche for incomplete bacterial clearance.

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