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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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Related in: MedlinePlus

L-arginine metabolism is correlated with the inhibition activity of MDSCs.Levels of (A) L-arginine, (B) Ornithine and (C) Nitrate in the serum of healthy donors (HD, N.15) and active TB patients (TB, N.30). Results are expressed as the median ± IQR. *P<0.05 **P<0.02.
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pone.0123772.g003: L-arginine metabolism is correlated with the inhibition activity of MDSCs.Levels of (A) L-arginine, (B) Ornithine and (C) Nitrate in the serum of healthy donors (HD, N.15) and active TB patients (TB, N.30). Results are expressed as the median ± IQR. *P<0.05 **P<0.02.

Mentions: It was previously shown that MDSCs from TB patients may exert their suppressive function by arginase-I (Arg-I) [13–15]; however, a clear demonstration is missing. To evaluate whether Arg-I activity plays a role during TB infection, we tested the plasma level of its substrate L-arginine by HPLC. We observed that the concentration of this amino acid is lower in the plasma of TB patients compared to HD (Fig 3A), suggesting a higher activity of Arg-I. However, L-arginine serves as a substrate for two enzymes: iNOS, which generate NO, and arginase-I, which converts L-arginine to urea and L-ornithine. To evaluate which enzyme is involved in the arginine catabolism, we analyzed the concentration of NO and ornithine in the plasma of TB patients and healthy donors. We found a higher amount of NO in TB patients compared to HD (Fig 3B). On the contrary, no difference in the ornithine level between TB patients and healthy donors was observed (Fig 3C). These data indicate that in TB patients, iNOS is responsible for L-arginine degradation, suggesting that MDSCs could exert their suppression by iNOS activity.


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)

L-arginine metabolism is correlated with the inhibition activity of MDSCs.Levels of (A) L-arginine, (B) Ornithine and (C) Nitrate in the serum of healthy donors (HD, N.15) and active TB patients (TB, N.30). 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.g003: L-arginine metabolism is correlated with the inhibition activity of MDSCs.Levels of (A) L-arginine, (B) Ornithine and (C) Nitrate in the serum of healthy donors (HD, N.15) and active TB patients (TB, N.30). Results are expressed as the median ± IQR. *P<0.05 **P<0.02.
Mentions: It was previously shown that MDSCs from TB patients may exert their suppressive function by arginase-I (Arg-I) [13–15]; however, a clear demonstration is missing. To evaluate whether Arg-I activity plays a role during TB infection, we tested the plasma level of its substrate L-arginine by HPLC. We observed that the concentration of this amino acid is lower in the plasma of TB patients compared to HD (Fig 3A), suggesting a higher activity of Arg-I. However, L-arginine serves as a substrate for two enzymes: iNOS, which generate NO, and arginase-I, which converts L-arginine to urea and L-ornithine. To evaluate which enzyme is involved in the arginine catabolism, we analyzed the concentration of NO and ornithine in the plasma of TB patients and healthy donors. We found a higher amount of NO in TB patients compared to HD (Fig 3B). On the contrary, no difference in the ornithine level between TB patients and healthy donors was observed (Fig 3C). These data indicate that in TB patients, iNOS is responsible for L-arginine degradation, suggesting that MDSCs could exert their suppression by iNOS activity.

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