Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells

Vollbrecht, Thomas; Stirner, Renate; Tufman, Amanda; Roider, Julia; Huber, Rudolf M.; Bogner, Johannes R.; Lechner, Andreas; Bourquin, Carole; Draenert, Rika

doi:10.1097/qad.0b013e328354b43f

Cited by 137 publications

(201 citation statements)

References 18 publications

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“…Vollbrecht et al (2012) showed that chronically HIV-infected HAART-naive individuals had significantly higher MDSC levels than healthy controls which was positively correlated with the viral load and negatively correlated with CD4 + T cell count. Qin et al (2013) found a significant increase of MDSCs in HIV-1-seropositive patients in comparison with healthy controls even in the presence of efficient anti-retroviral therapy.…”

Section: Mdscs As a Target For Diseases Of Ageingmentioning

confidence: 97%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.

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Section: Mdscs As a Target For Diseases Of Ageingmentioning

confidence: 97%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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“…Beyond P. aeruginosa, these findings may have a broader relevance for infections with flagellated bacteria in general, such as Helicobacter pylori, Salmonella typhimurium, or flagellated Escherichia coli strains. The flagellin-induced upregulation of the G-protein-coupled receptor CXCR4 on MDSCs could pave the way to target this leukocyte subset pharmacologically, using small-molecule inhibitors and underpins, with CXCR4 as HIV coreceptor, a potential role for MDSCs in HIV infection (50). Our observation that flagellin induced CXCR4 high MDSCs, but that CXCR4 was dispensable for MDSC-mediated T cell suppression, may further suggest that CXCR4 in this setting may play a role in MDSC functionality beyond T cell suppression, such as MDSC migration, homing, or survival.…”

Section: Discussionmentioning

confidence: 99%

Flagellin Induces Myeloid-Derived Suppressor Cells: Implications for Pseudomonas aeruginosa Infection in Cystic Fibrosis Lung Disease

Rieber

Brand

Hector

et al. 2013

The Journal of Immunology

116

127

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Pseudomonas aeruginosa persists in patients with cystic fibrosis (CF) and drives CF lung disease progression. P. aeruginosa potently activates the innate immune system, mainly mediated through pathogen-associated molecular patterns, such as flagellin. However, the host is unable to eradicate this flagellated bacterium efficiently. The underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells generated in cancer and proinflammatory microenvironments and are capable of suppressing T cell responses. We hypothesized that P. aeruginosa induces MDSCs to escape T cell immunity. In this article, we demonstrate that granulocytic MDSCs accumulate in CF patients chronically infected with P. aeruginosa and correlate with CF lung disease activity. Flagellated P. aeruginosa culture supernatants induced the generation of MDSCs, an effect that was 1) dose-dependently mimicked by purified flagellin protein, 2) significantly reduced using flagellin-deficient P. aeruginosa bacteria, and 3) corresponded to TLR5 expression on MDSCs in vitro and in vivo. Both purified flagellin and flagellated P. aeruginosa induced an MDSC phenotype distinct from that of the previously described MDSC-inducing cytokine GM-CSF, characterized by an upregulation of the chemokine receptor CXCR4 on the surface of MDSCs. Functionally, P. aeruginosa–infected CF patient ex vivo–isolated as well as flagellin or P. aeruginosa in vitro–generated MDSCs efficiently suppressed polyclonal T cell proliferation in a dose-dependent manner and modulated Th17 responses. These studies demonstrate that flagellin induces the generation of MDSCs and suggest that P. aeruginosa uses this mechanism to undermine T cell–mediated host defense in CF and other P. aeruginosa–associated chronic lung diseases.

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“…Accumulating evidence has demonstrated that MDSCs were closely associated with disease progression in malignancy and some inflammation-mediated pathological conditions (7,16). Although recent studies report MDSC expansion in viral infections (17)(18)(19)(20)(21)(22), phenotypic and functional features of MDSCs are still poorly defined in patients with CHB. The aim of this study was to determine whether MDSCs are involved in the impaired immune response leading to chronic HBV infection.…”

Section: Hla-drmentioning

confidence: 99%

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

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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.

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Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells

Abstract: We conclude that chronic uncontrolled HIV-infection is associated with elevated levels of MDSC, which potentially contribute to the impaired T-cell responses characteristic for the progressive disease stage.

Cited by 137 publications

References 18 publications

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Flagellin Induces Myeloid-Derived Suppressor Cells: Implications for Pseudomonas aeruginosa Infection in Cystic Fibrosis Lung Disease

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

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