Spatial profiling of tuberculosis granulomas from non-human primates reveals that the myeloid core is partitioned into two distinct metabolic zones, one of which is hypoxic. Hypoxia is associated with dysfunctional immune cell states and altered spatial organization, including lymphocyte exclusion, and may be a driver of impaired immunity in tuberculosis.
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References
Pagán, A. J. & Ramakrishnan, L. The formation and function of granulomas. Annu. Rev. Immunol. 36, 639–665 (2018). A review article that provides an overview of TB granulomas, describing the steps of granuloma formation and factors that drive disparate outcomes.
McCaffrey, E. F. et al. The immunoregulatory landscape of human tuberculosis granulomas. Nat. Immunol. 23, 318–329 (2022). This paper uses multiplexed imaging of human TB granulomas, finding they contain immunosuppressive features akin to tumors.
Gideon, H. P. et al. Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control. Immunity 55, 827–846.e10 (2022). A paper that reports the cellular and molecular correlates of granuloma bacterial control in the non-human primate model of TB.
Keren, L. et al. MIBI-TOF: a multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci. Adv. 5, eaax5851 (2019). A paper describing the MIBI-TOF platform used in our study.
Haley, M. J. et al. Hypoxia coordinates the spatial landscape of myeloid cells within glioblastoma to affect survival. Sci. Adv. 10, (2024). A paper reporting on a similar phenomenon of hypoxia-induced cellular organization in glioblastoma.
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This is a summary of: McCaffrey, E. F. et al. The immunometabolic topography of cellular organization and bacterial control in tuberculosis granulomas. Nat. Immunol. https://doi.org/10.1038/s41590-026-02431-8 (2026).
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Hypoxia shapes immune cell organization and bacterial control in tuberculosis granulomas. Nat Immunol 27, 654–655 (2026). https://doi.org/10.1038/s41590-026-02466-x
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DOI: https://doi.org/10.1038/s41590-026-02466-x
