Monocyte Programmed Death Ligand-1, A Predicator for 28-Day Mortality in Septic Patients

Tai, Huiyu; Xing, Hailin; Xiao, Dong; Zhu, Zhaowei; Mei, Haifeng; Sun, Wenbin; Zhang, Wei

doi:10.1016/j.amjms.2017.12.008

Cited by 14 publications

(11 citation statements)

References 30 publications

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“…It was defined on monocytes, macrophages and endothelial cells (34) but not granulocytes. Monocyte PD-L1 expression was described as an independent predictor of 28-day mortality in patients with septic shock (18,19). Peripheral blood transcriptomic analysis done by Uhle et al, revealed the expression of PD-L1-gene among the top 44 immune-related genes differentially expressed between patients with sepsis and healthy donors (11).…”

Section: Discussionmentioning

confidence: 99%

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Two new immature and dysfunctional neutrophil cell subsets define a predictive signature of sepsis useable in clinical practice

Meghraoui-Kheddar

Chousterman

Guillou

et al. 2020

Preprint

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One Sentence Summary:CD123 + and/or PD-L1 + immature and dysfunctional neutrophil subsets identified by mass cytometry, define an early human blood signature of sepsis Abstract:Sepsis is the leading cause of death in adult intensive care units. At present, sepsis diagnosis relies on non-specific clinical features. It could transform clinical care to have objective immune cell biomarkers that could predict sepsis diagnosis and guide treatment. For decades, neutrophil phenotypes have been studied in sepsis, but a diagnostic cell subset has yet to be identified. Here, high dimensional mass cytometry was used to reveal for the first time a specific neutrophil signature of sepsis severity that does not overlap with other inflammatory biomarkers, and that distinguishes patients with sepsis from those with non-infectious inflammatory syndrome. Unsupervised analysis of 42-dimesional mass cytometry data characterized previously unappreciated heterogeneity within the CD64 + immature neutrophils and revealed two new subsets distinguished by CD123 and PD-L1 expression. These immature neutrophils exhibited diminished activation and phagocytosis functions.The proportion of CD123-expressing neutrophils also correlated with clinical severity. Critically, this study showed that these two new neutrophil subsets were specific to sepsis and detectable by routine flow cytometry using seven markers. The demonstration here that a simple blood test distinguishes sepsis from other inflammatory conditions represents a key biological milestone that can be immediately translated into improvements in patient care.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies identified also the interleukin (IL)-3 as an orchestrator of emergency myelopoiesis during sepsis, and showed its association with hospital mortality (17,18). In parallel, programmed death ligand-1 (PD-L1) expressed on monocytes was also described as a mortality-predictor in sepsis patients (18,19).…”

Section: Introductionmentioning

confidence: 97%

Two new immature and dysfunctional neutrophil cell subsets define a predictive signature of sepsis useable in clinical practice

Meghraoui-Kheddar

Chousterman

Guillou

et al. 2020

Preprint

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“…Monocyte subsets differ for their ability to present antigens and produce pro‐inflammatory cytokines, as well as to express specific homing receptors. Interestingly, they can upregulate the so‐called inhibitory receptors belonging to the family of immune checkpoints, such as PD‐1 and its ligands (including PD‐L1), in several pathological conditions (Zasada et al , 2017; Wang et al , 2017; Tai et al , 2018; Riva & Mehta, 2019).…”

Section: Introductionmentioning

confidence: 99%

Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia

et al. 2020

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In patients infected by SARS-CoV-2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood monocytes from patients with COVID-19 pneumonia and found that these cells show signs of altered bioenergetics and mitochondrial dysfunction, had a reduced basal and maximal respiration, reduced spare respiratory capacity, and decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting reduced capability to perform aerobic glycolysis. Although COVID-19 monocytes had a reduced ability to perform oxidative burst, they were still capable of producing TNF and IFN-c in vitro. A significantly high amount of monocytes had depolarized mitochondria and abnormal mitochondrial ultrastructure. A redistribution of monocyte subsets, with a significant expansion of intermediate/pro-inflammatory cells, and high amounts of immature monocytes were found, along with a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints like PD-1/PD-L1. High plasma levels of several inflammatory cytokines and chemokines, including GM-CSF, IL-18, CCL2, CXCL10, and osteopontin, finally confirm the importance of monocytes in COVID-19 immunopathogenesis.

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“…T-cell exhaustion, through the crosstalk between immune checkpoint (IC) ligands expressed on monocytes and macrophages surfaces and their counterparts on T cells, is the main mechanism through which this immunosuppressive phenotype occurs (9). In this regard, we and other authors have demonstrated the role of Programmed cell death-protein 1 (PD-1) and its ligand (PD-L1) in this context (10)(11)(12)(13)).…”

Section: Introductionmentioning

confidence: 72%

SIGLEC5: An immune checkpoint ligand in sepsis

Lozano-Rodríguez¹,

Avendaño-Ortíz²,

Montalbán-Hernández³

et al. 2020

Preprint

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Sepsis is a global health priority. Despite thorough studies in mice models, its molecular and cellular basis remain unclear and there is no pharmacological effective treatment other than antimicrobial and supportive therapy. During sepsis, T cells exhaustion compromises patients outcome, and immune checkpoints (ICs) become crucial players in disease management. Here, a total of 425 patients with systemic inflammatory response criteria and 127 controls were studied. Soluble SIGLEC5 (sSIGLEC5) levels in plasma were higher in patients with sepsis compared to the other groups and even higher in those patients with septic-shock. sSIGLEC5 plasma levels were higher in non-survivors than in survivors and ROC curves analysis revealed sSIGLEC5 as a survival marker (cut-off ≤ 523.6 ng/mL). In vitro experiments illustrated how SIGLEC5 impaired CD8+ proliferation through binding to PSGL1. Blocking the SIGLEC5/PSGL1 axis reverted the latter effect. Mechanistically, SIGLEC5 overexpression was driven by HIF1α. Exogenous sSIGLEC5 accelerated death and magnified acute lung injury in mice models. Our data demonstrates how plasma sSIGLEC5 level on admission predicts death and stratifies patients with sepsis. This molecule exhibits the hallmarks of an IC ligand.

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Monocyte Programmed Death Ligand-1, A Predicator for 28-Day Mortality in Septic Patients

Cited by 14 publications

References 30 publications

Two new immature and dysfunctional neutrophil cell subsets define a predictive signature of sepsis useable in clinical practice

Two new immature and dysfunctional neutrophil cell subsets define a predictive signature of sepsis useable in clinical practice

Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia

SIGLEC5: An immune checkpoint ligand in sepsis

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