scholarly journals Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

2020 ◽  
Author(s):  
Tomohiro Takano ◽  
Takayuki Matsumura ◽  
Yu Adachi ◽  
Kazutaka Terahara ◽  
Saya Moriyama ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Flow Cytometric Analysis ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Recovery Phase ◽  
Cell Compartment ◽  
Cell Dynamics ◽  
Flow Cytometric ◽  
Myeloid Derived Suppressor Cell ◽  
Plasma Cytokines

Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19); however, it remains unclear whether myeloid cells are beneficial or detrimental to the clinical outcome. Here, we tracked cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis by flow cytometric analysis of blood samples from COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, rather than other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Notably, this subset was selectively expanded in survivors of severe cases and diminished during recovery. Analysis of plasma cytokines/chemokines revealed that interleukin-8 increased prior to PMN-MDSC expansion in survivors and returned to basal levels during the recovery phase. In contrast, interleukin-6 and interferon-g-induced protein 10 were abundantly induced in non-survivors, suggesting possible downstream targets for the immunosuppressive effects of the MDSC subset. Our data indicate that increased cellularity of PMN-MDSCs might be beneficial for the clinical outcome and could be useful as a possible predictor of prognosis in cases of severe COVID-19.

scholarly journals Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

2020 ◽  
Author(s):  
Tomohiro Takano ◽  
Takayuki Matsumura ◽  
Yu Adachi ◽  
Kazutaka Terahara ◽  
Saya Moriyama ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Flow Cytometric Analysis ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Recovery Phase ◽  
Cell Compartment ◽  
Cell Dynamics ◽  
Flow Cytometric ◽  
Myeloid Derived Suppressor Cell ◽  
Plasma Cytokines

Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19); however, it remains unclear whether myeloid cells are beneficial or detrimental to the clinical outcome. Here, we tracked cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis by flow cytometric analysis of blood samples from COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, rather than other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Notably, this subset was selectively expanded in survivors of severe cases and diminished during recovery. Analysis of plasma cytokines/chemokines revealed that interleukin-8 increased prior to PMN-MDSC expansion in survivors and returned to basal levels during the recovery phase. In contrast, interleukin-6 and interferon--induced protein 10 were abundantly induced in non-survivors, suggesting possible downstream targets for the immunosuppressive effects of the MDSC subset. Our data indicate that increased cellularity of PMN-MDSCs might be beneficial for the clinical outcome and could be useful as a possible predictor of prognosis in cases of severe COVID-19.

scholarly journals Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

2020 ◽  
Author(s):  
Tomohiro Takano ◽  
Takayuki Matsumura ◽  
Yu Adachi ◽  
Kazutaka Terahara ◽  
Saya Moriyama ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Flow Cytometric Analysis ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Recovery Phase ◽  
Cell Compartment ◽  
Cell Dynamics ◽  
Flow Cytometric ◽  
Myeloid Derived Suppressor Cell ◽  
Plasma Cytokines

Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19); however, it remains unclear whether myeloid cells are beneficial or detrimental to the clinical outcome. Here, we tracked cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis by flow cytometric analysis of blood samples from COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, rather than other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Notably, this subset was selectively expanded in survivors of severe cases and diminished during recovery. Analysis of plasma cytokines/chemokines revealed that interleukin-8 increased prior to PMN-MDSC expansion in survivors and returned to basal levels during the recovery phase. In contrast, interleukin-6 and interferon--induced protein 10 were abundantly induced in non-survivors, suggesting possible downstream targets for the immunosuppressive effects of the MDSC subset. Our data indicate that increased cellularity of PMN-MDSCs might be beneficial for the clinical outcome and could be useful as a possible predictor of prognosis in cases of severe COVID-19.

scholarly journals Myeloid cell dynamics correlating with clinical outcomes of severe COVID-19 in Japan

2021 ◽  
Author(s):  
Tomohiro Takano ◽  
Takayuki Matsumura ◽  
Yu Adachi ◽  
Kazutaka Terahara ◽  
Saya Moriyama ◽  
...  
Keyword(s):  
Cell Expansion ◽  
Cohort Analysis ◽  
Cell Subset ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Mortality Rates ◽  
Cell Compartment ◽  
Cell Dynamics ◽  
Japanese Cohort ◽  
Myeloid Derived Suppressor Cell

Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with interleukin 8 (IL-8) levels prior to the cell expansion, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Thus, our data indicates that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan.

scholarly journals Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
McKenzie K. Hollen ◽  
Julie A. Stortz ◽  
Dijoia Darden ◽  
Marvin L. Dirain ◽  
Dina C. Nacionales ◽  
...  
Keyword(s):  
Cell Function ◽  
Expression Patterns ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Myeloid Derived Suppressor Cell ◽  
T Lymphocyte Proliferation ◽  
Suppressive Phenotype ◽  
Sepsis Survivors ◽  
Over Time

Abstract Background Sepsis is an increasingly significant challenge throughout the world as one of the major causes of patient morbidity and mortality. Central to the host immunologic response to sepsis is the increase in circulating myeloid-derived suppressor cells (MDSCs), which have been demonstrated to be present and independently associated with poor long-term clinical outcomes. MDSCs are plastic cells and potentially modifiable, particularly through epigenetic interventions. The objective of this study was to determine how the suppressive phenotype of MDSCs evolves after sepsis in surgical ICU patients, as well as to identify epigenetic differences in MDSCs that may explain these changes. Methods Circulating MDSCs from 267 survivors of surgical sepsis were phenotyped at various intervals over 6 weeks, and highly enriched MDSCs from 23 of these samples were co-cultured with CD3/CD28-stimulated autologous T cells. microRNA expression from enriched MDSCs was also identified. Results We observed that MDSC numbers remain significantly elevated in hospitalized sepsis survivors for at least 6 weeks after their infection. However, only MDSCs obtained at and beyond 14 days post-sepsis significantly suppressed T lymphocyte proliferation and IL-2 production. These same MDSCs displayed unique epigenetic (miRNA) expression patterns compared to earlier time points. Conclusions We conclude that in sepsis survivors, immature myeloid cell numbers are increased but the immune suppressive function specific to MDSCs develops over time, and this is associated with a specific epigenome. These findings may explain the chronic and persistent immune suppression seen in these subjects.

P0934THE IMPACT OF HAEMODIALYSIS INITIATION ON CKD-ASSOCIATED MYELOID CELL DYSREGULATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sarah Cormican ◽  
Serika Diane Naicker ◽  
Denise Connolly ◽  
Gemma Prendergast ◽  
M Conall Dennedy ◽  
...  
Keyword(s):  
Flow Cytometric Analysis ◽  
Myeloid Cell ◽  
Absolute Number ◽  
Flow Cytometer ◽  
Dialysis Initiation ◽  
Monocyte Subset ◽  
Cell Lineages ◽  
Flow Cytometric ◽  
The Absolute ◽  
Population Numbers

Abstract Background and Aims Abnormalities of the myeloid immune cell lineages are well described in people with both Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD). Increased numbers and proportions of the intermediate (CD14++CD16+) and nonclassical (CD14+CD16+) monocyte subsets and increased neutrophil numbers have been reported in both settings. These changes are one aspect of the chronic inflammatory state which exists in people with CKD and ESRD and which contributes to complications including cardiovascular disease and protein-energy malnutrition. The effects of transition from advanced CKD to dialysis on myeloid cell populations has not been well studied. We investigated these changes by measuring major leucocyte population numbers and monocyte subset numbers and proportions in adults with Stage 5 CKD prior to and after haemodialysis initiation. Method Adults with stage 5 CKD and a non-emergent indication for dialysis initiation (in-centre haemodialysis) were recruited after informed consent. Blood samples were collected within the week prior to dialysis initiation and follow-up samples were collected prior to a dialysis session at one week and one month after haemodialysis initiation. Major leucocyte population numbers were determined by two-colour flow cytometric analysis of whole blood on an Accuri™ Flow Cytometer. Peripheral blood mononuclear cells were isolated and stained for multi-colour flow cytometric analysis on a Canto II™ flow cytometer. The absolute number of each monocyte subset/ml blood was calculated based on the above values. Results Ten individuals (six male, four female) with a mean age of 78 ± 6.4years were enrolled and completed all follow-ups. The mean eGFR was 9 ± 1.9ml/min at the time of haemodialysis initiation. Total monocyte numbers had not changed after one month of haemodialysis (Figure 1A) (3.6x105 ± 1.6x105cells/ml) compared to initiation (5.2x105 ± 3.2x105, p=0.11). However, the proportion of nonclassical monocytes was markedly increased after one week of haemodialysis (16.8% (IQR 12.8-21.0%) compared to 11.2% (IQR 9.3-12.3%) at initiation, p=0.007) (Figure 1B). At one month the proportion of nonclassical monocytes was maintained (17.1% (IQR 14.5-20.5%)) but had not increased further compared to the one week timepoint (p=0.97). This proportionate change was not reflected in the absolute nonclassical count. There were no significant changes in the proportion of classical or intermediate monocytes. Neutrophil numbers were reduced at one month (3.6x106 ± 1.3x106cells/ml) compared to initiation (4.8X106 ± 1.6x106cells/ml, p=0.04) (Figure 1A). Total lymphocyte numbers did not change significantly after dialysis initiation. Conclusion Haemodialysis initiation is associated with an increase in the proportion of nonclassical monocytes without significant increases in the absolute number of any monocyte subset. A reduction in total neutrophil number also occurs one month after dialysis initiation. It has been previously been shown that progression of CKD results in increasing abnormalities of the myeloid cell lineages. Here we have demonstrated that transition from advanced CKD to haemodialysis results in further modulation of myeloid cell numbers and myeloid cell subset proportions.

scholarly journals Cholangiocarcinoma presents a distinct myeloid-derived suppressor cell signature compared to other hepatobiliary cancers

2019 ◽  
Author(s):  
Defne Bayik ◽  
Adam J. Lauko ◽  
Gustavo A. Roversi ◽  
Emily Serbinowski ◽  
Lou-Anne Acevedo-Moreno ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
The Cancer Genome Atlas ◽  
Limiting Factor ◽  
Isocitrate Dehydrogenase 1 ◽  
Myeloid Derived Suppressor Cell ◽  
Liver Cancers ◽  
Malignant Liver ◽  
Immunosuppressive Cells

AbstractMyeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSC in other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). Investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of the Cancer Genome Atlas demonstrated that a high MDSC score in HCC patients predicted poor disease outcome. Mechanistic studies indicated that the oncometabolite D-2-hydroxyglutarate resulting from isocitrate dehydrogenase 1 mutation could be a limiting factor of MDSC accumulation in CCA patients. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, they may comprise suitable targets for effective immunotherapy approaches.

scholarly journals Hepatobiliary malignancies have distinct peripheral myeloid-derived suppressor cell signatures and tumor myeloid cell profiles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Defne Bayik ◽  
Adam J. Lauko ◽  
Gustavo A. Roversi ◽  
Emily Serbinowski ◽  
Lou-Anne Acevedo-Moreno ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
The Cancer Genome Atlas ◽  
Hepatobiliary Malignancies ◽  
Myeloid Derived Suppressor Cell ◽  
Liver Cancers ◽  
Malignant Liver ◽  
Immunosuppressive Cells ◽  
Antigen Presenting

Abstract Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSCs in the peripheral blood of patients with other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), and colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). The investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions, suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of The Cancer Genome Atlas dataset demonstrated that a high MDSC score in HCC patients is associated with poor disease outcome. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, these cells may represent suitable targets for effective immunotherapy approaches.

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