Lack of Significant Elevation of Myeloid-Derived Suppressor Cells in Peripheral Blood of Chronically Hepatitis C Virus-Infected Individuals

Nonnenmann, Julia; Stirner, Renate; Roider, Julia; Jung, M; Schrödl, Kathrin; Bogner, Johannes R.; Draenert, Rika

doi:10.1128/jvi.00113-14

Cited by 18 publications

(15 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in contrast with these studies, Nonnenmann and colleagues (33) showed that MDSCs in peripheral blood are not of significance for immune dysfunction in chronic hepatitis C. We postulated that the differences in frequency and suppressive capacity of MDSCs might partly result from different MDSC subsets and various HCV genotypes. Therefore, the precise role of MDSCs in chronic virus infection and their associations with outcome remain elusive.…”

Section: Discussionmentioning

confidence: 61%

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Huang

Zhang

Yan

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Although myeloid-derived suppressor cells (MDSCs) are well known for their immunosuppressive function in several pathological conditions, the role of MDSCs in hepatitis B virus infection remains obscure. In this study, we investigated the frequency and function of MDSCs in the peripheral blood and liver of 91 chronic hepatitis B (CHB) patients. A higher percentage of MDSCs, defined as CD14+HLA-DR−/low, was detected in peripheral blood of CHB patients than that of the healthy controls. Moreover, high expression of programmed death 1 (PD-1) and secretion of IL-10 in this population were determined. The frequency of MDSCs was positively correlated with serum viral load, but it was negatively correlated with liver inflammatory injury. These cells were also abundant in liver tissue of CHB patients and were related to necroinflammatory activity. Furthermore, we found that these cells could suppress hepatitis B virus–specific CD8+ T cell response, including reduced proliferation and IFN-γ production, and inhibit degranulation of CD8+ T cells, including reduced production of granzyme B and perforin. Importantly, PD-1–induced IL-10 production by MDSCs was responsible for the suppressive activity. To our knowledge, for the first time our study proved that CD14+HLA-DR–/lowPD-1+ MDSCs in CHB patients contribute to an inadequate immune response against the virus and lead to chronic infection, which represents a potential target for therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 61%

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Huang

Zhang

Yan

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…However, the role of MDSCs in viral persistence or latency remains controversial and far from clear. For example, while some studies have shown that monocytic MDSCs are remarkably elevated and play a role in the pathogenesis of HIV or HCV infection [13-15, 40-42], Bowers et al [16] reported an immune suppression by neutrophils during HIV-1 infection; whereas Nonnenmann et al [43] found no significant increases in MDSCs and lack of their suppressive functions in peripheral blood of chronically HCV-infected individuals. We postulated that these discrepancies in MDSC frequency and suppressive capability might partially result from measuring different MDSC subsets, using different methodologies, investigating different patient populations and/or focusing on different disease stages with specific cytokine milieus that may induce distinct MDSC phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Expansion of myeloid-derived suppressor cells promotes differentiation of regulatory T cells in HIV-1+ individuals

Wang

Zhao

Ren

et al. 2016

Aids

View full text Add to dashboard Cite

Objective Regulatory T cells (Tregs) contribute to HIV-1 disease progression by impairing antiviral immunity; however, the precise mechanisms responsible for the development of Tregs in the setting of HIV-1 infection are incompletely understood. Design In this study, we provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3+ Tregs. Methods We measured MDSC induction and cytokine expression by flow cytometry and analyzed their functions by co-culturing experiments. Results We observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1+) individuals, even in those on antiretroviral therapy (ART) with undetectable viremia, when compared to healthy subjects. We also observed increases in M-MDSCs after incubating healthy peripheral mononuclear cells (PBMCs) with HIV-1 proteins (gp120 or Tat) or Toll-like receptor (TLR) 4 ligand Lipopolysaccharides (LPS) in vitro, an effect that could be abrogated in the presence of the pSTAT-3 inhibitor, STA-21. Functional analyses indicated that M-MDSCs from HIV-1+ individuals express higher levels of IL-10, TGF-β, IL-4Rα, p47phex, PD-L1, and pSTAT-3 – all of which are known mediators of myelopoiesis and immunosuppression. Importantly, incubation of healthy CD4+ T cells with MDSCs derived from HIV-1+ individuals significantly increased differentiation of Foxp3+ Tregs. In addition, depletion of MDSCs from PBMCs of HIV-1+ individuals led to a significant reduction of Foxp3+ Tregs and increase of IFN-γ production by CD4+ T effector cells (Teffs). Conclusions These results suggest that HIV-induced MDSCs promote Treg cell development and inhibit T cell function - a hallmark of many chronic infectious diseases.

show abstract

“…Indeed, inconsistent results for MDSCs in various virus infections were not rare among previous studies [5]. A study by Nonnenmann et al [38] reported that peripheral MDSCs were not significantly increased in patients with chronic HCV infection, and there was no difference in MDSC based on genotype or viral load, and a similar effect was found for suppression the function of CD8 + T cells. In another study, mMDSCs were observed to be unrelated to HCV RNA loads, and levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) [39].…”

Section: Discussionmentioning

confidence: 52%

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

Lu¹,

Li²,

Lin³

et al. 2017

J Antivir Antiretrovir

View full text Add to dashboard Cite

Both human leukocyte antigen-G (HLA-G) and myeloid-derived suppressor cells (MDSCs) was associated with the pathogenesis of infectious diseases. Whether peripheral MDSCs express HLA-G during virus infection remains unknown. We investigated the frequency of HLA-G + MDSCs and its subsets in patients infected with chronic hepatitis B (CHB). In this study, frequencies of peripheral MDSCs (Lin1-HLA-DR-CD33 + CD11b + ) and HLA-G expressing subsets from 50 CHB patients and 27 normal controls were analyzed using flow cytometry. Data revealed the median percentage of MDSCs was not significantly different between the CHB patients and controls (0.30% vs. 0.29%; p=0.884). Among MDSCs, similar frequency was observed for CD14+ monocytic MDSC (mMDSCs; 31.25% vs. 23.35%; p=0.063) and CD15 + granulocytic MDSC (gMDSCs; 22.60% vs. 21.55%; p=0.558) between the two groups. However, HLA-G + MDSCs was significantly increased in CHB patients compared with that of controls (3.30% vs. 0.50%; p<0.001). Furthermore, both HLA-G + mMDSCs (0.99% vs. 0.00%; p<0.001) and HLA-G + gMDSC (0.78% vs. 0.00%; p<0.001) were also dramatically increased in CHB patients. Particularly, HLA-G + gMDSC was inversely correlated to the viral DNA loads and significantly increased in HBeAb positive patients. Summary, this work reports for the first time HLA-G + MDSCs, a new population of peripheral MDSCs, were expanded in CHB patients; however, its clinical relevance yet to be further explored.

show abstract

Lack of Significant Elevation of Myeloid-Derived Suppressor Cells in Peripheral Blood of Chronically Hepatitis C Virus-Infected Individuals

Cited by 18 publications

References 14 publications

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Expansion of myeloid-derived suppressor cells promotes differentiation of regulatory T cells in HIV-1+ individuals

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

Contact Info

Product

Resources

About