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Myeloid-Derived Suppressor Cells Mediate T Cell Dysfunction in Nonhuman Primate TB Granulomas
Bindu Singh1, Dhiraj K Singh1, Shashank R Ganatra1
1Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.
Myeloid-derived suppressor cells (MDSCs) are more abundant and immunosuppressive in active tuberculosis (TB), localizing to granuloma periphery. Their presence may indicate active TB or successful therapy, suggesting MDSCs as a therapeutic target.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Myeloid-derived suppressor cells (MDSCs) are potent immunosuppressive innate immune cells.
- MDSCs are found in active tuberculosis (TB) patients but their lung localization is unclear.
- Nonhuman primates (NHPs) offer a relevant model for studying human pulmonary TB granulomas.
Purpose of the Study:
- To investigate the role and localization of MDSCs in latent TB infection (LTBI) and active TB (ATB) using an NHP model.
- To characterize the immunosuppressive functions and cellular markers of MDSCs in pulmonary TB.
Main Methods:
- Utilized a nonhuman primate model to study pulmonary tuberculosis.
- Quantified and characterized granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in lungs.
- Assessed PMN-MDSC proliferation, expansion, and immunosuppressive markers (Ki67, IDO1, IL-10, MMP-9, iNOS, PD-L1).
Main Results:
- Higher proportions of PMN-MDSCs were found in ATB lungs compared to LTBI or naive controls.
- Active TB lungs showed increased PMN-MDSC proliferation and immunosuppressive marker expression.
- Immunosuppressive PMN-MDSCs were localized to the periphery of granulomas in ATB, not in the core.
Conclusions:
- PMN-MDSCs play a significant immunomodulatory role in ATB by restricting T cell access to granulomas.
- MDSC presence could serve as a biomarker for ATB, and their reduction may indicate treatment success.
- MDSCs represent a potential cellular target for adjunctive TB therapies.
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