University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Microbiology and Physiological Systems

Publication Date

2021-04-18

Document Type

Article Preprint

Disciplines

Bacterial Infections and Mycoses | Bacteriology | Immunology of Infectious Disease | Immunopathology

Abstract

Mycobacterium tuberculosis lung infection results in a complex multicellular structure, the granuloma. In some granulomas, immune activity promotes bacterial clearance; in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque granulomas by co-registering longitudinal PET-CT imaging, single-cell RNA-sequencing, and measures of bacterial clearance. Bacterial control associates with the dynamics of granuloma formation and cellular composition. Early granulomas have limited capacity for bacterial restriction and are characterized by Type 2 immune features—plasma cells, mast cells, and IL-4/13 signaling. Granulomas that emerge after the onset of adaptive responses exhibit superior bacterial killing and are enriched for hybrid Type1-Type17 and certain cytotoxic T cells—host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.

Keywords

lung granulomas, tuberculosis, Immunology

Rights and Permissions

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

DOI of Published Version

10.1101/2020.10.24.352492

Source

bioRxiv 2020.10.24.352492; doi: https://doi.org/10.1101/2020.10.24.352492. Link to preprint on bioRxiv.

Comments

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

The PDF available for download is Version # of this preprint. The complete version history of this preprint is available at bioRxiv.

Full author list omitted for brevity. For the full list of authors, see article.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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