The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report
IntroductionProtective host responses in those exposed to or infected with tuberculosis (TB) is thought to require a delicate balance between pro-inflammatory and regulatory immune responses. Myeloid-derived suppressor cells (MDSCs), regulatory cells that dampen T-cell function, have been described...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.676679/full |
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| author | Malika Davids Anil Pooran Liezel Smith Liezel Smith Michele Tomasicchio Keertan Dheda Keertan Dheda |
| author_facet | Malika Davids Anil Pooran Liezel Smith Liezel Smith Michele Tomasicchio Keertan Dheda Keertan Dheda |
| author_sort | Malika Davids |
| collection | DOAJ |
| description | IntroductionProtective host responses in those exposed to or infected with tuberculosis (TB) is thought to require a delicate balance between pro-inflammatory and regulatory immune responses. Myeloid-derived suppressor cells (MDSCs), regulatory cells that dampen T-cell function, have been described in cancer and other infectious diseases but there are limited data on their role in TB.MethodsPeripheral blood was obtained from patients with active pulmonary TB and participants with presumed latent TB infection (LTBI) from Cape Town, South Africa. MDSC frequency was ascertained by flow cytometry. Purified MDSCs were used to assess (i) their suppressive effect on T-cell proliferation using a Ki67 flow cytometric assay and (ii) their effect on mycobacterial containment by co-culturing with H37Rv-infected monocyte-derived macrophages and autologous pre-primed effector T-cells with or without MDSCs. Mycobacterial containment was measured by plating colony forming units (CFU).ResultsMDSCs (CD15+HLA-DR-CD33+) had significantly higher median frequencies (IQR) in patients with active TB (n=10) versus LTBI (n= 10) [8.2% (6.8-10.7) versus 42.2% (27–56) respectively; p=0.001]. Compared to MDSC-depleted peripheral blood mononuclear and effector T cell populations, dilutions of purified MDSCs isolated from active TB patients suppressed T-cell proliferation by up to 72% (n=6; p=0.03) and significantly subverted effector T-cell-mediated containment of H37Rv in monocyte-derived macrophages (n=7; 0.6% versus 8.5%; p=0.02).ConclusionCollectively, these data suggest that circulating MDSCs are induced during active TB disease and can functionally suppress T-cell proliferation and subvert mycobacterial containment. These data may inform the design of vaccines and immunotherapeutic interventions against TB but further studies are required to understand the mechanisms underpinning the effects of MDSCs. |
| first_indexed | 2024-12-19T00:44:36Z |
| format | Article |
| id | doaj.art-15938e435d934516ac04e5727caf4845 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T00:44:36Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-15938e435d934516ac04e5727caf48452022-12-21T20:44:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.676679676679The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary ReportMalika Davids0Anil Pooran1Liezel Smith2Liezel Smith3Michele Tomasicchio4Keertan Dheda5Keertan Dheda6Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South AfricaCentre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South AfricaCentre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South AfricaDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaCentre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South AfricaCentre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South AfricaDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomIntroductionProtective host responses in those exposed to or infected with tuberculosis (TB) is thought to require a delicate balance between pro-inflammatory and regulatory immune responses. Myeloid-derived suppressor cells (MDSCs), regulatory cells that dampen T-cell function, have been described in cancer and other infectious diseases but there are limited data on their role in TB.MethodsPeripheral blood was obtained from patients with active pulmonary TB and participants with presumed latent TB infection (LTBI) from Cape Town, South Africa. MDSC frequency was ascertained by flow cytometry. Purified MDSCs were used to assess (i) their suppressive effect on T-cell proliferation using a Ki67 flow cytometric assay and (ii) their effect on mycobacterial containment by co-culturing with H37Rv-infected monocyte-derived macrophages and autologous pre-primed effector T-cells with or without MDSCs. Mycobacterial containment was measured by plating colony forming units (CFU).ResultsMDSCs (CD15+HLA-DR-CD33+) had significantly higher median frequencies (IQR) in patients with active TB (n=10) versus LTBI (n= 10) [8.2% (6.8-10.7) versus 42.2% (27–56) respectively; p=0.001]. Compared to MDSC-depleted peripheral blood mononuclear and effector T cell populations, dilutions of purified MDSCs isolated from active TB patients suppressed T-cell proliferation by up to 72% (n=6; p=0.03) and significantly subverted effector T-cell-mediated containment of H37Rv in monocyte-derived macrophages (n=7; 0.6% versus 8.5%; p=0.02).ConclusionCollectively, these data suggest that circulating MDSCs are induced during active TB disease and can functionally suppress T-cell proliferation and subvert mycobacterial containment. These data may inform the design of vaccines and immunotherapeutic interventions against TB but further studies are required to understand the mechanisms underpinning the effects of MDSCs.https://www.frontiersin.org/articles/10.3389/fimmu.2021.676679/fullmyeloid derived suppressor cellsMDSCtuberculosisimmunologybiomarkers |
| spellingShingle | Malika Davids Anil Pooran Liezel Smith Liezel Smith Michele Tomasicchio Keertan Dheda Keertan Dheda The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report Frontiers in Immunology myeloid derived suppressor cells MDSC tuberculosis immunology biomarkers |
| title | The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report |
| title_full | The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report |
| title_fullStr | The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report |
| title_full_unstemmed | The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report |
| title_short | The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report |
| title_sort | frequency and effect of granulocytic myeloid derived suppressor cells on mycobacterial survival in patients with tuberculosis a preliminary report |
| topic | myeloid derived suppressor cells MDSC tuberculosis immunology biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.676679/full |
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