scholarly journals TLR7 Ligation Inhibits TLR8 Responsiveness in IL-27-Primed Human THP-1 Monocytes and Macrophages

2021 ◽  
pp. 1-14
Author(s):  
Natalya Odoardi ◽  
Olena Kourko ◽  
Carlene Petes ◽  
Sameh Basta ◽  
Katrina Gee
Keyword(s):  
Myeloid Cell ◽  
Cytokine Expression ◽  
Virus Infections ◽  
Chemokine Production ◽  
Ssrna Virus ◽  
Monocytes And Macrophages ◽  
The Face ◽  
Mrna And Protein Expression ◽  
And Function ◽  
Bacterial Sensing

Regulation of proinflammatory cytokine expression is critical in the face of single-stranded RNA (ssRNA) virus infections. Many viruses, including coronavirus and influenza virus, wreak havoc on the control of cytokine expression, leading to the formation of detrimental cytokine storms. Understanding the regulation and interplay between inflammatory cytokines is critical to the identification of targets involved in controlling the induction of cytokine expression. In this study, we focused on how the antiviral cytokine interleukin-27 (IL-27) regulates signal transduction downstream of Toll-like receptor 7 (TLR7) and TLR8 ligation, which recognize endosomal single-stranded RNA. Given that IL-27 alters bacterial-sensing TLR expression on myeloid cells and can inhibit replication of single-stranded RNA viruses, we investigated whether IL-27 affects expression and function of TLR7 and TLR8. Analysis of IL-27-treated THP-1 monocytic cells and THP-1-derived macrophages revealed changes in mRNA and protein expression of TLR7 and TLR8. Although treatment with IL-27 enhanced TLR7 expression, only TLR8-mediated cytokine secretion was amplified. Furthermore, we demonstrated that imiquimod, a TLR7 agonist, inhibited cytokine and chemokine production induced by a TLR8 agonist, TL8-506. Delineating the immunomodulatory role of IL-27 on TLR7 and TLR8 responses provides insight into how myeloid cell TLR-mediated responses are regulated during virus infection.

scholarly journals A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease

2017 ◽  
Author(s):  
Kuan-lin Huang ◽  
Edoardo Marcora ◽  
Anna A Pimenova ◽  
Antonio F Di Narzo ◽  
Manav Kapoor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Function ◽  
Age At Onset ◽  
Myeloid Cell ◽  
Cell Types ◽  
A Genome ◽  
Monocytes And Macrophages ◽  
And Function

AbstractA genome-wide survival analysis of 14,406 Alzheimer’s disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and fourteen novel loci associated with age at onset. LD score regression of 220 cell types implicated regulation of myeloid gene expression in AD risk. In particular, the minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability is enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affect the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function.

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Felix Clemens Richter ◽  
Aljawharah Alrubayyi ◽  
Alicia Teijeira Crespo ◽  
Sarah Hulin-Curtis ◽  
Keyword(s):  
Lipid Metabolism ◽  
Influenza A ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Low Grade ◽  
Obese Patients ◽  
Healthy Weight ◽  
Virus Infections ◽  
Immune Alterations ◽  
And Function

Abstract The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host’s altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

scholarly journals The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages

2018 ◽  
Vol 12 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Stanislas Grassin-Delyle ◽  
Charlotte Abrial ◽  
Hélène Salvator ◽  
Marion Brollo ◽  
Emmanuel Naline ◽  
...  
Keyword(s):  
Human Lung ◽  
Macrophage Phenotype ◽  
Chemokine Production ◽  
Lung Macrophages ◽  
Cytokines And Chemokines ◽  
M1 Macrophage ◽  
Microbial Infections ◽  
Selective Agonists ◽  
And Function ◽  
Subtype Selective

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype.

miR‐223 promotes regenerative myeloid cell phenotype and function in the demyelinated central nervous system

Glia ◽  
2018 ◽  
Vol 67 (5) ◽  
pp. 857-869 ◽  
Author(s):  
Dylan A. Galloway ◽  
Stephanie N. Blandford ◽  
Tangyne Berry ◽  
John B. Williams ◽  
Mark Stefanelli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Myeloid Cell ◽  
Cell Phenotype ◽  
And Function

scholarly journals Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats

2016 ◽  
Vol 40 (1-2) ◽  
pp. 347-360 ◽  
Author(s):  
Jing Zhang ◽  
Sheng Jun An ◽  
Jun Qiu Fu ◽  
Pei Liu ◽  
Tie Mei Shao ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Hypertensive Rats ◽  
Active Ingredients ◽  
Spontaneously Hypertensive ◽  
Sd Rats ◽  
Mrna And Protein Expression ◽  
And Function ◽  
And Oxidative Stress ◽  
Tgf Β1 ◽  
Cardiovascular Functions

Background/Aims: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat various cardiovascular diseases in traditional Chinese medicine, the efficacy and function of optimal compatibility ratio of SM's active ingredients (SABP) in the prevention and treatment of cardiovascular diseases remain uncertain. This study investigated antihypertensive effect and underlying mechanisms of SABP vs. SM lyophilized powder (SMLP) in spontaneously hypertensive rats (SHR) and to establish the ratio of the optimal compatibility of DSS, Sal-A, Sal-B and PAL in improving cardiovascular functions. Methods: The SHRs were treated with either SABP or SMLP and their systolic blood pressures (SBP) were monitored. The isolated thoracic aorta of SHRs was segregated for immunohistochemistry, Hematoxylin-Eosin stain and mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1, α-SMA and Smad7. Moreover, the adventitial fibroblasts (AFs) were isolated and cultured from SD rats' aorta and the reactive oxygen species (ROS) production was determined after SABP or SMLP treatment. Results: SABP, but not SMLP, significantly reduced SBP, which were accompanied by the inhibited morphological changes in the thoracic aorta and the reduced mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1 and α-SMA, but the increased Smad 7 expression in SHRs. Moreover, SABP also resulted in a decreased ROS production in AFs of SD rats. Conclusions: These results indicate that SABP, but not SMLP, treatment potently inhibits hypertension through improvements of vascular remodeling and oxidative stress. The present study provides new evidence that the efficacy and function from optimal compatibility ratio of SM active ingredients is much better than its lyophilized powder, which represents a strategy to develop SM's new beneficial effect in improving cardiovascular functions.

scholarly journals Neural contributors to trauma resilience: a review of longitudinal neuroimaging studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alyssa R. Roeckner ◽  
Katelyn I. Oliver ◽  
Lauren A. M. Lebois ◽  
Sanne J. H. van Rooij ◽  
Jennifer S. Stevens
Keyword(s):  
Individual Differences ◽  
Neural Circuit ◽  
Major Life ◽  
Stress Resilience ◽  
Control Networks ◽  
The Face ◽  
Sensory Cortices ◽  
Life Stressor ◽  
Threat Cues ◽  
And Function

AbstractResilience in the face of major life stressors is changeable over time and with experience. Accordingly, differing sets of neurobiological factors may contribute to an adaptive stress response before, during, and after the stressor. Longitudinal studies are therefore particularly effective in answering questions about the determinants of resilience. Here we provide an overview of the rapidly-growing body of longitudinal neuroimaging research on stress resilience. Despite lingering gaps and limitations, these studies are beginning to reveal individual differences in neural circuit structure and function that appear protective against the emergence of future psychopathology following a major life stressor. Here we outline a neural circuit model of resilience to trauma. Specifically, pre-trauma biomarkers of resilience show that an ability to modulate activity within threat and salience networks predicts fewer stress-related symptoms. In contrast, early post-trauma biomarkers of subsequent resilience or recovery show a more complex pattern, spanning a number of major circuits including attention and cognitive control networks as well as primary sensory cortices. This novel synthesis suggests stress resilience may be scaffolded by stable individual differences in the processing of threat cues, and further buttressed by post-trauma adaptations to the stressor that encompass multiple mechanisms and circuits. More attention and resources supporting this work will inform the targets and timing of mechanistic resilience-boosting interventions.

scholarly journals NetFACS: Using network science to understand facial communication systems

2021 ◽  
Author(s):  
Alexander Mielke ◽  
Bridget M. Waller ◽  
Claire Pérez ◽  
Alan V. Rincon ◽  
Julie Duboscq ◽  
...  
Keyword(s):  
Network Analysis ◽  
Communication Systems ◽  
Network Science ◽  
Coding System ◽  
Communication Tool ◽  
Resampling Methods ◽  
Facial Movements ◽  
The Face ◽  
Analyse Data ◽  
And Function

AbstractUnderstanding facial signals in humans and other species is crucial for understanding the evolution, complexity, and function of the face as a communication tool. The Facial Action Coding System (FACS) enables researchers to measure facial movements accurately, but we currently lack tools to reliably analyse data and efficiently communicate results. Network analysis can provide a way to use the information encoded in FACS datasets: by treating individual AUs (the smallest units of facial movements) as nodes in a network and their co-occurrence as connections, we can analyse and visualise differences in the use of combinations of AUs in different conditions. Here, we present ‘NetFACS’, a statistical package that uses occurrence probabilities and resampling methods to answer questions about the use of AUs, AU combinations, and the facial communication system as a whole in humans and non-human animals. Using highly stereotyped facial signals as an example, we illustrate some of the current functionalities of NetFACS. We show that very few AUs are specific to certain stereotypical contexts; that AUs are not used independently from each other; that graph-level properties of stereotypical signals differ; and that clusters of AUs allow us to reconstruct facial signals, even when blind to the underlying conditions. The flexibility and widespread use of network analysis allows us to move away from studying facial signals as stereotyped expressions, and towards a dynamic and differentiated approach to facial communication.

scholarly journals Inteligentne rozwiązania w miastach w czasie pandemii - wybrane obszary, funkcje i zastosowania

e-mentor ◽  
2021 ◽  
Vol 88 (1) ◽  
pp. 55-63
Author(s):  
Dominika P. Brodowicz ◽  
Keyword(s):  
Climate Change ◽  
Urban Areas ◽  
Public Institutions ◽  
Healthcare Sector ◽  
Virus Infections ◽  
State Of Emergency ◽  
Safety And Health ◽  
The World ◽  
The Face ◽  
Modern Technologies

Today's cities face many challenges, including those related to the aging of the population, climate change, or broadly understood public safety and health. Examples from many places around the world show that without access to modern technologies, cities, companies, and public institutions could not function, provide services or care for the safety of billions of people living in urban areas. That is especially vital in conditions of the threat to many people's health and life and shutdown of economies caused by the coronavirus SARS-CoV-2. Therefore, the article aims to present selected examples of smart solutions used in cities in the face of the challenges related to ensuring security. Their functionality in pandemic conditions is also described both at present and if the state of emergency continued for the following years. The study proved that the importance of smart solutions for contemporary cities' functioning is growing in the face of the threat to the residents' health and life caused by COVID-19. That mainly applies to tools in the area of e-government, e-education, and e-services in the healthcare sector, including applications for reporting and informing about clusters of virus infections.

scholarly journals Agrin is required for survival and function of monocytic cells

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5502-5511 ◽  
Author(s):  
Cristina Mazzon ◽  
Achille Anselmo ◽  
Cristiana Soldani ◽  
Javier Cibella ◽  
Cristina Ploia ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Synapse Formation ◽  
Myeloid Cell ◽  
Heparan Sulfate Proteoglycans ◽  
Extracellular Matrix Protein ◽  
Monocytic Cells ◽  
Hematopoietic System ◽  
Extracellular Signal ◽  
And Function

Abstract Agrin, an extracellular matrix protein belonging to the heterogeneous family of heparan sulfate proteoglycans (HSPGs), is expressed by cells of the hematopoietic system but its role in leukocyte biology is not yet clear. Here we demonstrate that agrin has a crucial, nonredundant role in myeloid cell development and functions. We have identified lineage-specific alterations that affect maturation, survival and properties of agrin-deficient monocytic cells, and occur at stages later than stem cell precursors. Our data indicate that the cell-autonomous signals delivered by agrin are sensed by macrophages through the α-DC (DG) receptor and lead to the activation of signaling pathways resulting in rearrangements of the actin cytoskeleton during the phagocytic synapse formation and phosphorylation of extracellular signal-regulated kinases (Erk 1/2). Altogether, these data identify agrin as a novel player of innate immunity.

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