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Granulocytic myeloid derived suppressor cells expansion during active pulmonary tuberculosis is associated with high nitric oxide plasma level.

El Daker S, Sacchi A, Tempestilli M, Carducci C, Goletti D, Vanini V, Colizzi V, Lauria FN, Martini F, Martino A - PLoS ONE (2015)

Bottom Line: We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma.We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB.Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Immunology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy; Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France; Department of Biology, University of Rome Tor Vergata, Rome, Italy.

ABSTRACT
Tuberculosis (TB) is still the principal cause of death caused by a single infectious agent, and the balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. The aim of this work was to study the role of myeloid-derived suppressor cells (MDSCs) during active pulmonary tuberculosis at the site of infection. We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma. We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB. Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy.

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Peripheral blood CD14-CD11b+ MDSCs sorted by active TB patients suppress T-cell proliferation.PBMCs from TB patients were stimulated with CFSE labeled PBMC derived from healthy donors in the presence of sorted CD14-CD11b+ MDSCs at different ratios for 5 days. The percentage indicates the number of CD3+ T-cells which have undergone cellular division after 5 days. Results are expressed as the median ± IQR of three independent experiments. *P<0.05, **P<0.02.
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pone.0123772.g002: Peripheral blood CD14-CD11b+ MDSCs sorted by active TB patients suppress T-cell proliferation.PBMCs from TB patients were stimulated with CFSE labeled PBMC derived from healthy donors in the presence of sorted CD14-CD11b+ MDSCs at different ratios for 5 days. The percentage indicates the number of CD3+ T-cells which have undergone cellular division after 5 days. Results are expressed as the median ± IQR of three independent experiments. *P<0.05, **P<0.02.

Mentions: We used a MLR experiment to test the ability of MDSCs derived from the blood of TB patients to suppress proliferation of T-cells derived from HD. MDSC-depleted PBMCs (TB), treated with mitomycin C, were cultured with allogeneic CFSE-labeled PBMCs from HD (CFSE-labeled PBMCs (HD)) and with sorted CD14-CD11b+CD33+ HLA-DRlow/- MDSCs (MDSCs (TB)) at different ratios (1:2, 1:4 and 1:8). We observed that while HD T cells proliferate in presence of allogeneic TB PBMC MDSC-depleted, the addition of MDSC population from TB patients dramatically suppressed the T-cells proliferation in a dose-dependent manner (Fig 2).


Granulocytic myeloid derived suppressor cells expansion during active pulmonary tuberculosis is associated with high nitric oxide plasma level.

El Daker S, Sacchi A, Tempestilli M, Carducci C, Goletti D, Vanini V, Colizzi V, Lauria FN, Martini F, Martino A - PLoS ONE (2015)

Peripheral blood CD14-CD11b+ MDSCs sorted by active TB patients suppress T-cell proliferation.PBMCs from TB patients were stimulated with CFSE labeled PBMC derived from healthy donors in the presence of sorted CD14-CD11b+ MDSCs at different ratios for 5 days. The percentage indicates the number of CD3+ T-cells which have undergone cellular division after 5 days. Results are expressed as the median ± IQR of three independent experiments. *P<0.05, **P<0.02.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400140&req=5

pone.0123772.g002: Peripheral blood CD14-CD11b+ MDSCs sorted by active TB patients suppress T-cell proliferation.PBMCs from TB patients were stimulated with CFSE labeled PBMC derived from healthy donors in the presence of sorted CD14-CD11b+ MDSCs at different ratios for 5 days. The percentage indicates the number of CD3+ T-cells which have undergone cellular division after 5 days. Results are expressed as the median ± IQR of three independent experiments. *P<0.05, **P<0.02.
Mentions: We used a MLR experiment to test the ability of MDSCs derived from the blood of TB patients to suppress proliferation of T-cells derived from HD. MDSC-depleted PBMCs (TB), treated with mitomycin C, were cultured with allogeneic CFSE-labeled PBMCs from HD (CFSE-labeled PBMCs (HD)) and with sorted CD14-CD11b+CD33+ HLA-DRlow/- MDSCs (MDSCs (TB)) at different ratios (1:2, 1:4 and 1:8). We observed that while HD T cells proliferate in presence of allogeneic TB PBMC MDSC-depleted, the addition of MDSC population from TB patients dramatically suppressed the T-cells proliferation in a dose-dependent manner (Fig 2).

Bottom Line: We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma.We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB.Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Immunology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy; Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France; Department of Biology, University of Rome Tor Vergata, Rome, Italy.

ABSTRACT
Tuberculosis (TB) is still the principal cause of death caused by a single infectious agent, and the balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. The aim of this work was to study the role of myeloid-derived suppressor cells (MDSCs) during active pulmonary tuberculosis at the site of infection. We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma. We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB. Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy.

Show MeSH
Related in: MedlinePlus