Department of Microbiology and Physiological Systems
Bacterial Infections and Mycoses | Bacteriology | Immunology of Infectious Disease | Immunopathology
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.
lung granulomas, tuberculosis, Immunology
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DOI of Published Version
bioRxiv 2020.10.24.352492; doi: https://doi.org/10.1101/2020.10.24.352492. Link to preprint on bioRxiv.
Gideon HP, Behar SM, Flynn JL, Fortune SM, Shalek AK. (2021). Multimodal profiling of lung granulomas reveals cellular correlates of tuberculosis 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/2018
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