Role of myeloid derived suppressor cells in sepsis

Malavika, M.; Sanju, S.; Poorna, M.R.; Priya, V. Vishnu; Sidharthan, Neeraj; Varma, Praveen Kerala; Mony, Ullas

doi:10.1016/j.intimp.2021.108452

Cited by 16 publications

(19 citation statements)

References 51 publications

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“…Both animal models and all clinical studies to date uncovered that high proportions of MDSCs were associated with clinical worsening in infectious diseases along with sepsis [25,26]. In line with the previous study, we found that neutrophils percentage is positively correlated with circulating MDSCs subsets frequency and C-reactive protein (CRP) level is especially positively correlated with circulating M-MDSC frequency.…”

Section: Discussionsupporting

confidence: 88%

The Distribution of Myeloid-Derived Suppressor Cells subsets and Up-regulation of Programmed Death-1/PD-L1 axis in Peripheral Blood of Adult CAP Patients

Gong

Zhao

et al. 2022

Preprint

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Background: Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of CAP. Methods: The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. Results: PBMCs from CAP patients contained an elevated frequency of both G-MDSC (4.92+0.30 vs 2.25+0.21,p<0.0001) and M-MDSC (19.40+1.30 vs 9.64+0.57,p<0.001) compared to healthy controls. Treg cells in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note,the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. Conclusions: In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated Treg dysfunction at least partially in CAP patients .

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Section: Discussionsupporting

confidence: 88%

The Distribution of Myeloid-Derived Suppressor Cells subsets and Up-regulation of Programmed Death-1/PD-L1 axis in Peripheral Blood of Adult CAP Patients

Gong

Zhao

et al. 2022

Preprint

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“…These cells are transiently released by the haematopoietic machinery during many inflammatory responses. However, if this MDSC expansion and its tissue infiltration persist, it can induce lymphopenia and immunoparalysis [34].…”

Section: Discussionmentioning

confidence: 99%

Immunoparalysis in critically ill children

et al. 2022

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Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university‐affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)‐DR expression and tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 production were measured by flow‐cytometry at three time points (T1 = 1–2 days; T2 = 3–5 days; T3 = 6–8 days). Using the paediatric logistic organ dysfunction‐2 score to assess initial disease severity, we established the optimal cut‐off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA‐DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL‐6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA‐DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF‐α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non‐classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA‐DR expression with lower frequencies of monocytes producing TNF‐α and IL‐6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non‐classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.

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“…The two main myeloid-derived suppressor cell (MDSC) subsets are monocytic and granulocyte (G)-MDSC; the latter has the phenotype CD33 + CD11b + CD14 + HLA-DR low [ 307 ]. Thus, G-MDSCs represent a subset or a further neutrophil differentiation/development.…”

Section: Several Molecular Markers Of Neutrophil Heterogeneity Are In...mentioning

confidence: 99%

“…Thus, G-MDSCs represent a subset or a further neutrophil differentiation/development. Several neutrophil-secreted cytokines can function as expanders of MDSCs, and the TLR-target NFκB can function as an MDSC activator [ 307 ].…”

Section: Several Molecular Markers Of Neutrophil Heterogeneity Are In...mentioning

confidence: 99%

The Regulation of Neutrophil Migration in Patients with Sepsis: The Complexity of the Molecular Mechanisms and Their Modulation in Sepsis and the Heterogeneity of Sepsis Patients

Bruserud

Mosevoll

Bruserud

et al. 2023

Cells

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Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Common causes include gram-negative and gram-positive bacteria as well as fungi. Neutrophils are among the first cells to arrive at an infection site where they function as important effector cells of the innate immune system and as regulators of the host immune response. The regulation of neutrophil migration is therefore important both for the infection-directed host response and for the development of organ dysfunctions in sepsis. Downregulation of CXCR4/CXCL12 stimulates neutrophil migration from the bone marrow. This is followed by transmigration/extravasation across the endothelial cell barrier at the infection site; this process is directed by adhesion molecules and various chemotactic gradients created by chemotactic cytokines, lipid mediators, bacterial peptides, and peptides from damaged cells. These mechanisms of neutrophil migration are modulated by sepsis, leading to reduced neutrophil migration and even reversed migration that contributes to distant organ failure. The sepsis-induced modulation seems to differ between neutrophil subsets. Furthermore, sepsis patients should be regarded as heterogeneous because neutrophil migration will possibly be further modulated by the infecting microorganisms, antimicrobial treatment, patient age/frailty/sex, other diseases (e.g., hematological malignancies and stem cell transplantation), and the metabolic status. The present review describes molecular mechanisms involved in the regulation of neutrophil migration; how these mechanisms are altered during sepsis; and how bacteria/fungi, antimicrobial treatment, and aging/frailty/comorbidity influence the regulation of neutrophil migration.

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Role of myeloid derived suppressor cells in sepsis

Cited by 16 publications

References 51 publications

The Distribution of Myeloid-Derived Suppressor Cells subsets and Up-regulation of Programmed Death-1/PD-L1 axis in Peripheral Blood of Adult CAP Patients

The Distribution of Myeloid-Derived Suppressor Cells subsets and Up-regulation of Programmed Death-1/PD-L1 axis in Peripheral Blood of Adult CAP Patients

Immunoparalysis in critically ill children

The Regulation of Neutrophil Migration in Patients with Sepsis: The Complexity of the Molecular Mechanisms and Their Modulation in Sepsis and the Heterogeneity of Sepsis Patients

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