P127: The ratio of intermediate/non‐classical monocytes is increased in women with infertility and recurrent pregnancy losses

Abstract Background After successful cardiopulmonary resuscitation with return of spontaneous circulation (ROSC), many patients show signs of an overactive immune activation. Monocytes are a heterogenous cell population that can be distinguished into three subsets. Purpose The aim of this prospective, observational study was to analyze whether monocyte subset distribution is associated with mortality at 6 months in patients after cardiac arrest. Methods We included 53 patients admitted to our medical ICU after cardiac arrest. Blood was taken on admission and monocyte subset distribution was analyzed by flow cytometry and distinguished into classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+CCR2+) and non-classical monocytes (NCM; CD14+CD16++CCR2-). Results Median age was 64.5 (IQR 49.8–74.3) years and 75.5% of patients were male. Mortality at 6 months was 50.9% and survival with good neurological outcome was 37.7%. Of interest, monocyte subset distribution upon admission to the ICU did not differ according to survival. However, patients that died within 6 months showed a strong increase in the pro-inflammatory subset of intermediate monocytes (8.3% (3.8–14.6)% vs. 4.1% (1.5–8.2)%; p=0.025), and a decrease of classical monocytes (87.5% (79.9–89.0)% vs. 90.8% (85.9–92.7)%; p=0.036) 72 hours after admission. In addition, intermediate monocytes were predictive of outcome independent of initial rhythm and time to ROSC and correlated with the CPC-score at 6 months (R=0.32; p=0.043). Discussion Monocyte subset distribution is associated with outcome in patients surviving a cardiac arrest. This suggests that activation of the innate immune system may play a significant role in patient outcome after cardiac arrest. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FWF - Fonds zur Förderung der wissenschaftlichen Forschung

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Glucocerebrosidase Activity is Reduced in Cryopreserved Parkinson’s Disease Patient Monocytes and Inversely Correlates with Motor Severity

Journal of Parkinson s Disease ◽

10.3233/jpd-202508 ◽

2021 ◽

pp. 1-9

Author(s):

Laura P. Hughes ◽

Marilia M.M. Pereira ◽

Deborah A. Hammond ◽

John B. Kwok ◽

Glenda M. Halliday ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Rating Scale ◽

Disease Patient ◽

Motor Symptom ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Classical Monocytes

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.

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Decreased classical monocytes and CD163 expression in TB patients: an indicator of drug resistance

Brazilian Journal of Microbiology ◽

10.1007/s42770-021-00454-x ◽

2021 ◽

Author(s):

Faheem Shahzad ◽

Noman Bashir ◽

Atia Ali ◽

Shagufta Jabeen ◽

Mohammad Kashif ◽

...

Keyword(s):

Drug Resistance ◽

Cd163 Expression ◽

Classical Monocytes

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S02.2: PD‐1/PD‐L1 expression in women with unexplained recurrent pregnancy losses and obstetrical complications

American Journal of Reproductive Immunology ◽

10.1111/aji.26_13417 ◽

2021 ◽

Vol 85 (S1) ◽

pp. 28-28

Keyword(s):

Obstetrical Complications ◽

Recurrent Pregnancy Losses

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Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with monocyte subsets in patients with stable coronary artery disease

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.278 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

KA Krychtiuk ◽

M Lenz ◽

P Hohensinner ◽

K Distelmaier ◽

L Schrutka ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

Lipid Lowering ◽

Monocyte Subsets ◽

Proprotein Convertase ◽

Artery Disease ◽

Circulating Levels ◽

Classical Monocytes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

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Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

Nature Communications ◽

10.1038/s41467-021-21414-x ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Melanie R. Neeland ◽

Samantha Bannister ◽

Vanessa Clifford ◽

Kate Dohle ◽

Kim Mulholland ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Immune Responses ◽

Acute Phase ◽

Innate Immune ◽

Low Density ◽

Innate Immune Responses ◽

Immunological Mechanisms ◽

Activated Neutrophils ◽

Classical Monocytes

AbstractChildren have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

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Resolvin D1 reduces cancer growth stimulating a protective neutrophil-dependent recruitment of anti-tumor monocytes

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01937-3 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Domenico Mattoscio ◽

Elisa Isopi ◽

Alessia Lamolinara ◽

Sara Patruno ◽

Alessandro Medda ◽

...

Keyword(s):

Cancer Cells ◽

Growth Curve ◽

Immune Cells ◽

Cancer Growth ◽

Resolvin D1 ◽

Anti Cancer ◽

Classical Monocytes ◽

Human And Mouse

Abstract Background Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression. Methods Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients. Results RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration. Conclusions RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.

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Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients

Scientific Reports ◽

10.1038/s41598-021-85148-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chandra Chiappin Cardoso ◽

Camila Matiollo ◽

Carolina Hilgert Jacobsen Pereira ◽

Janaina Santana Fonseca ◽

Helder Emmanuel Leite Alves ◽

...

Keyword(s):

Dendritic Cells ◽

Liver Cirrhosis ◽

Liver Disease ◽

Dendritic Cell ◽

Disease Severity ◽

Advanced Liver Disease ◽

Hla Dr ◽

Acute Decompensation ◽

Cirrhotic Patients ◽

Classical Monocytes

AbstractLiver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.

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Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte Subsets Contributes to Viral Burden in Humans

Journal of Virology ◽

10.1128/jvi.02735-15 ◽

2015 ◽

Vol 90 (5) ◽

pp. 2195-2207 ◽

Cited By ~ 28

Author(s):

Maria Fernanda de Castro-Amarante ◽

Cynthia A. Pise-Masison ◽

Katherine McKinnon ◽

Robyn Washington Parks ◽

Veronica Galli ◽

...

Keyword(s):

T Cells ◽

Leukemia Virus ◽

Receptor Expression ◽

Monocyte Subsets ◽

Viral Dna ◽

Cell Leukemia Virus Type ◽

Human T Cell ◽

T Cell Leukemia Virus ◽

Classical Monocytes ◽

Intermediate Monocytes

ABSTRACTBecause the viral DNA burden correlates with disease development, we investigated the contribution of monocyte subsets (classical, intermediate, and nonclassical monocytes) to the total viral burden in 22 human T cell leukemia virus type 1 (HTLV-1)-infected individuals by assessing their infectivity status, frequency, as well as chemotactic and phagocytic functions. All three monocyte subsets sorted from HTLV-1-infected individuals were positive for viral DNA, and the frequency of classical monocytes was lower in the blood of HTLV-1-infected individuals than in that of uninfected individuals, while the expression levels of the chemokine receptors CCR5, CXCR3, and CX3CR1 in classical monocytes were higher in HTLV-1-infected individuals than uninfected individuals; the percentage of intermediate monocytes and their levels of chemokine receptor expression did not differ between HTLV-1-infected and uninfected individuals. However, the capacity of intermediate monocytes to migrate to CCL5, the ligand for CCR5, was higher, and a higher proportion of nonclassical monocytes expressed CCR1, CXCR3, and CX3CR1. The level of viral DNA in the monocyte subsets correlated with the capacity to migrate to CCL2, CCL5, and CX3CL1 for classical monocytes, with lower levels of phagocytosis for intermediate monocytes, and with the level of viral DNA in CD8+and CD4+T cells for nonclassical monocytes. These data suggest a model whereby HTLV-1 infection augments the number of classical monocytes that migrate to tissues and become infected and the number of infected nonclassical monocytes that transmit virus to CD4+and CD8+T cells. These results, together with prior findings in a macaque model of HTLV-1 infection, support the notion that infection of monocytes by HTLV-1 is likely a requisite for viral persistence in humans.IMPORTANCEMonocytes have been implicated in immune regulation and disease progression in patients with HTLV-1-associated inflammatory diseases. We detected HTLV-1 DNA in all three monocyte subsets and found that infection impacts surface receptor expression, migratory function, and subset frequency. The frequency of nonclassical patrolling monocytes is increased in HTLV-1-infected individuals, and they have increased expression of CCR1, CXCR3, and CX3CR1. The viral DNA level in nonclassical monocytes correlated with the viral DNA level in CD4+and CD8+T cells. Altogether, these data suggest an increased recruitment of classical monocytes to inflammation sites that may result in virus acquisition and, in turn, facilitate virus dissemination and viral persistence. Our findings thus provide new insight into the importance of monocyte infection in viral spread and suggest targeting of monocytes for therapeutic intervention.

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