What question did this study set out to answer?

To identify the key drivers that establish an immunosuppressive niche within tuberculosis granulomas and assess whether the magnitude of this response associates with bacterial persistence.

February 23, 2025Open Access

The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control

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Authors

EMErin McCaffrey ADAlea Delmastro IFIsobel Fitzhugh

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Overview

Spatial analysis uncovers hypoxic microenvironments blocking lymphocyte infiltration in primate tuberculosis granulomas, highlighting hypoxia as a prime driver of bacterial persistence.

Key Points

To identify the key drivers that establish an immunosuppressive niche within tuberculosis granulomas and assess whether the magnitude of this response associates with bacterial persistence.
Conducted a multimodal spatial analysis of 52 granulomas from 16 non-human primates infected with low-dose Mycobacterium tuberculosis for 9 to 12 weeks.
Quantified the bacterial burden of each individual granuloma to evaluate the relationship between spatial architecture and pathogen control.
Revealed universal partitioning of the granuloma myeloid core into two distinct metabolic zones, with one region exhibiting severe hypoxia.
Associated the hypoxic zone with pathologic immune cell states, disrupted cellular organization, and a near-complete blockade of lymphocyte infiltration.
Determined that the magnitude of hypoxia-linked structural and cellular abnormalities directly correlated with elevated bacterial burden.

Cite This Study

McCaffrey et al. (2025) studied this question.

synapsesocial.com/papers/69daa422a6045d71bfa3d613 https://doi.org/10.1101/2025.02.18.638923

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February 23, 2025Open Access

The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control

View Full Paper

Ask AI

Bookmark

Authors

EMErin McCaffrey ADAlea Delmastro IFIsobel Fitzhugh

Discussion

Member takes

Overview

Spatial analysis uncovers hypoxic microenvironments blocking lymphocyte infiltration in primate tuberculosis granulomas, highlighting hypoxia as a prime driver of bacterial persistence.

Key Points

To identify the key drivers that establish an immunosuppressive niche within tuberculosis granulomas and assess whether the magnitude of this response associates with bacterial persistence.
Conducted a multimodal spatial analysis of 52 granulomas from 16 non-human primates infected with low-dose Mycobacterium tuberculosis for 9 to 12 weeks.
Quantified the bacterial burden of each individual granuloma to evaluate the relationship between spatial architecture and pathogen control.
Revealed universal partitioning of the granuloma myeloid core into two distinct metabolic zones, with one region exhibiting severe hypoxia.
Associated the hypoxic zone with pathologic immune cell states, disrupted cellular organization, and a near-complete blockade of lymphocyte infiltration.
Determined that the magnitude of hypoxia-linked structural and cellular abnormalities directly correlated with elevated bacterial burden.

Cite This Study

McCaffrey et al. (2025) studied this question.

synapsesocial.com/papers/69daa422a6045d71bfa3d613 https://doi.org/10.1101/2025.02.18.638923

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