University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2020-10-26
Document Type
Article Preprint
Disciplines
Bacterial Infections and Mycoses | Hemic and Lymphatic Diseases | Immunology and Infectious Disease | Microbiology | Respiratory Tract Diseases
Abstract
In humans and nonhuman primates, Mycobacterium tuberculosis lung infection yields a complex multicellular structure—the tuberculosis granuloma. All granulomas are not equivalent, however, even within the same host: in some, local immune activity promotes bacterial clearance, while in others, it allows persistence or outgrowth. Here, we used single-cell RNA-sequencing to define holistically cellular responses associated with control in cynomolgus macaques. Granulomas that facilitated bacterial killing contained significantly higher proportions of CD4+ and CD8+ T cells expressing hybrid Type1-Type17 immune responses or stem-like features and CD8-enriched T cells with specific cytotoxic functions; failure to control correlated with mast cell, plasma cell and fibroblast abundance. Co-registering these data with serial PET-CT imaging suggests that a degree of early immune control can be achieved through cytotoxic activity, but that more robust restriction only arises after the priming of specific adaptive immune responses, defining new targets for vaccination and treatment.
Keywords
tuberculosis, lung granulomas, lymphocytes, 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.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Gideon HP, Behar SM, Shalek A. (2020). Single-cell profiling of tuberculosis lung granulomas reveals functional lymphocyte signatures of bacterial control [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.10.24.352492. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1836
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Bacterial Infections and Mycoses Commons, Hemic and Lymphatic Diseases Commons, Immunology and Infectious Disease Commons, Microbiology Commons, Respiratory Tract Diseases Commons
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Full author list omitted for brevity. For the full list of authors, see article.