Spatial transcriptomics of pediatric tuberculosis lymph nodes reveals a conserved hypoxia_SPP1 niche
- 1South African Medical Research Council Centre for Tuberculosis Research, Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Heal
Abstract
Pediatric tuberculosis (TB) often presents as primary disease involving the mediastinal lymph nodes; however, its granuloma microenvironment remains poorly characterized because these population patient tissues are rarely available for study. Here, we use spatial transcriptomics to profile 60 granulomas from four children aged 4 to 36 months. We identified nine recurrent transcriptional microenvironments shared across granulomas, despite their marked histological heterogeneity. One macrophage-rich microenvironment showed strong hypoxia-associated activity and secreted phosphoprotein 1 (SPP1) enrichment. This microenvironment was present in both non-necrotic and necrotic lesions and overlapped with a Mtb-persistence macrophage signature previously identified in murine TB lymph nodes. Pathway analysis revealed the enrichment of both antimicrobial and regulatory programs within this microenvironment, suggesting partial immune control rather than uniform inflammatory or suppressive activity in this region. SPP1 expression was associated with regions enriched for both M1- and M2-like macrophages, suggesting a macrophage program that extends beyond conventional polarization classifications and may be influenced by the local granuloma microenvironment. We further observed a similar spatial association between hypoxia-associated activity and SPP1 expression in an independent adult TB dataset (pooled Spearman {rho}=0.65) and validated this association at protein level by multiplex immunofluorescence in our pediatric TB granuloma sample. Overall, this study identified a hypoxia-associated SPP1-enriched microenvironment that may contribute to incomplete bacterial clearance and could provide a framework for evaluating host-directed strategies to enhance sterilizing immunity without exacerbating tissue damage.
Related
- Spatial transcriptomics reveals epithelial-immune remodeling preceding malignant transformation of oral premalignant lesions
- Cellular-Resolution Spatial Transcriptomics Reveals Laminar VSMC Phenotypic Remodeling and a Hypoxic Medial Core in Human Thoracic Aortic Dissection
- Harmonised benchmarking of foundation models for single-cell and spatial transcriptomics reveals context-dependent generalisation
- Single-cell spatial transcriptomics of inherited retinal degeneration reveals broad and focal organization of disease responses
- Spatial transcriptomics reveals selective vulnerability of cardiac neural crest-derived glial cells in human myocardial infarction
BibTeX
@misc{adebiyi2026spatial,
title = {{Spatial transcriptomics of pediatric tuberculosis lymph nodes reveals a conserved hypoxia_SPP1 niche}},
author = {S. O. Adebiyi and P. Goussard and D. R. De Wet and J. T. Janson and T. Jooste and A. Shabangu and A. Dorhoi and S. Bondoc and M. Nekorchuk and M. C. Chao and S. M. Fortune and K. Busman-Sahay and J. D. Estes and E. A. Shamskhou and K. B. Urdahl and M. Y. Gerner and G. Walzl and N. Du Plessis},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762471},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762471v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Spatial transcriptomics of pediatric tuberculosis lymph nodes reveals a conserved hypoxia_SPP1 niche
AU - S. O. Adebiyi
AU - P. Goussard
AU - D. R. De Wet
AU - J. T. Janson
AU - T. Jooste
AU - A. Shabangu
AU - A. Dorhoi
AU - S. Bondoc
AU - M. Nekorchuk
AU - M. C. Chao
AU - S. M. Fortune
AU - K. Busman-Sahay
AU - J. D. Estes
AU - E. A. Shamskhou
AU - K. B. Urdahl
AU - M. Y. Gerner
AU - G. Walzl
AU - N. Du Plessis
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762471
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762471v1
AB - Pediatric tuberculosis (TB) often presents as primary disease involving the mediastinal lymph nodes; however, its granuloma microenvironment remains poorly characterized because these population patient tissues are rarely available for study. Here, we use spatial transcriptomics to profile 60 granulomas from four children aged 4 to 36 months. We identified nine recurrent transcriptional microenvironments shared across granulomas, despite their marked histological heterogeneity. One macrophage-rich microenvironment showed strong hypoxia-associated activity and secreted phosphoprotein 1 (SPP1) enrichment. This microenvironment was present in both non-necrotic and necrotic lesions and overlapped with a Mtb-persistence macrophage signature previously identified in murine TB lymph nodes. Pathway analysis revealed the enrichment of both antimicrobial and regulatory programs within this microenvironment, suggesting partial immune control rather than uniform inflammatory or suppressive activity in this region. SPP1 expression was associated with regions enriched for both M1- and M2-like macrophages, suggesting a macrophage program that extends beyond conventional polarization classifications and may be influenced by the local granuloma microenvironment. We further observed a similar spatial association between hypoxia-associated activity and SPP1 expression in an independent adult TB dataset (pooled Spearman {rho}=0.65) and validated this association at protein level by multiplex immunofluorescence in our pediatric TB granuloma sample. Overall, this study identified a hypoxia-associated SPP1-enriched microenvironment that may contribute to incomplete bacterial clearance and could provide a framework for evaluating host-directed strategies to enhance sterilizing immunity without exacerbating tissue damage.
ER -