Limits...
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.

Show MeSH

Related in: MedlinePlus

Frequency of granulocytic MDSCs in BALc and peripheral blood of active TB patients and HD.(A) Gating strategy used to analyze the frequency of MDSCs, and dot plots showing CD14 expression on cells from P1, bringing to front cells in P2 (MDSCs, gray). (B) MDSCs obtained by sorting were examined by light microscopy. Morphologic analyses of peripheral MDSCs showed substantial homogeneity, comprised only of subset exhibiting granulocytic characteristics. (C) MDSC frequency in PBMCs derived from healthy donors (N.15), contact TB (N.12) and active TB (N.30). (D) Frequency of MDSCs in BALc derived from TB patients (N.30) and individuals with pulmonary diseases not correlated with TB (No TB, N.8). Results are expressed as the median ± IQR. *P<0.05, **P<0.02.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4400140&req=5

pone.0123772.g001: Frequency of granulocytic MDSCs in BALc and peripheral blood of active TB patients and HD.(A) Gating strategy used to analyze the frequency of MDSCs, and dot plots showing CD14 expression on cells from P1, bringing to front cells in P2 (MDSCs, gray). (B) MDSCs obtained by sorting were examined by light microscopy. Morphologic analyses of peripheral MDSCs showed substantial homogeneity, comprised only of subset exhibiting granulocytic characteristics. (C) MDSC frequency in PBMCs derived from healthy donors (N.15), contact TB (N.12) and active TB (N.30). (D) Frequency of MDSCs in BALc derived from TB patients (N.30) and individuals with pulmonary diseases not correlated with TB (No TB, N.8). Results are expressed as the median ± IQR. *P<0.05, **P<0.02.

Mentions: Our aim was to evaluate whether the expansion of MDSCs previously observed in the peripheral blood from the pulmonary TB patients [18] also occurred in the lung. Therefore, the presence of MDSCs was evaluated in the PBMCs and BALc of TB patients by flow cytometry. MDSCs were identified as HLA-DR-/lowCD11b+CD33+. Granulocytic and monocytic subsets were identified by using CD14 and CD15, and confirmed by Hematoxylin and Eosin staining (Fig 1A and 1B). A higher frequency of CD11b+CD14-CD33+CD15+HLA-DRlow/- MDSCs (CD14- MDSCs) was observed in PBMCs from TB patients compared to healthy donors (Fig 1A and 1C). Moreover, when household contacts were evaluated, the proportion of MDSCs was comparable to healthy controls (Fig 1C). A significant accumulation of the same MDSC subset was found in the BALc of pulmonary TB patients compared to pulmonary diseases uncorrelated with TB (Fig 1D). In our studies, we did not observe any difference between smokers and non-smokers regarding the frequency of MDSCs (data not shown).


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)

Frequency of granulocytic MDSCs in BALc and peripheral blood of active TB patients and HD.(A) Gating strategy used to analyze the frequency of MDSCs, and dot plots showing CD14 expression on cells from P1, bringing to front cells in P2 (MDSCs, gray). (B) MDSCs obtained by sorting were examined by light microscopy. Morphologic analyses of peripheral MDSCs showed substantial homogeneity, comprised only of subset exhibiting granulocytic characteristics. (C) MDSC frequency in PBMCs derived from healthy donors (N.15), contact TB (N.12) and active TB (N.30). (D) Frequency of MDSCs in BALc derived from TB patients (N.30) and individuals with pulmonary diseases not correlated with TB (No TB, N.8). Results are expressed as the median ± IQR. *P<0.05, **P<0.02.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123772.g001: Frequency of granulocytic MDSCs in BALc and peripheral blood of active TB patients and HD.(A) Gating strategy used to analyze the frequency of MDSCs, and dot plots showing CD14 expression on cells from P1, bringing to front cells in P2 (MDSCs, gray). (B) MDSCs obtained by sorting were examined by light microscopy. Morphologic analyses of peripheral MDSCs showed substantial homogeneity, comprised only of subset exhibiting granulocytic characteristics. (C) MDSC frequency in PBMCs derived from healthy donors (N.15), contact TB (N.12) and active TB (N.30). (D) Frequency of MDSCs in BALc derived from TB patients (N.30) and individuals with pulmonary diseases not correlated with TB (No TB, N.8). Results are expressed as the median ± IQR. *P<0.05, **P<0.02.
Mentions: Our aim was to evaluate whether the expansion of MDSCs previously observed in the peripheral blood from the pulmonary TB patients [18] also occurred in the lung. Therefore, the presence of MDSCs was evaluated in the PBMCs and BALc of TB patients by flow cytometry. MDSCs were identified as HLA-DR-/lowCD11b+CD33+. Granulocytic and monocytic subsets were identified by using CD14 and CD15, and confirmed by Hematoxylin and Eosin staining (Fig 1A and 1B). A higher frequency of CD11b+CD14-CD33+CD15+HLA-DRlow/- MDSCs (CD14- MDSCs) was observed in PBMCs from TB patients compared to healthy donors (Fig 1A and 1C). Moreover, when household contacts were evaluated, the proportion of MDSCs was comparable to healthy controls (Fig 1C). A significant accumulation of the same MDSC subset was found in the BALc of pulmonary TB patients compared to pulmonary diseases uncorrelated with TB (Fig 1D). In our studies, we did not observe any difference between smokers and non-smokers regarding the frequency of MDSCs (data not shown).

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