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Viruses Feb 2014The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV) infection results from the systemic hematogenous... (Review)
Review
The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV) infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes are also known to play a key role in viral latency and life-long persistence. However, in order to utilize infected monocytes for viral spread and persistence, HCMV must overcome a number of monocyte biological hurdles, including their naturally short lifespan and their inability to support viral gene expression and replication. Our laboratory has shown that HCMV is able to manipulate the biology of infected monocytes in order to overcome these biological hurdles by inducing the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral gene expression and replication. In this current review, we describe the unique aspects of how HCMV promotes monocyte survival and differentiation by inducing a "finely-tuned" macrophage cell type following infection. Specifically, we describe the induction of a uniquely polarized macrophage subset from infected monocytes, which we argue is the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host.
Topics: Cell Differentiation; Cell Survival; Cytomegalovirus; Host-Pathogen Interactions; Humans; Macrophages; Monocytes
PubMed: 24531335
DOI: 10.3390/v6020782 -
Thrombosis Research Aug 2023Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical,...
INTRODUCTION
Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown.
METHODS
Monocytic tissue factor surface expression was investigated during three conditions. Primary human monocytes and microvascular endothelial cell co-cultures were used for in vitro studies. Volunteers received a bolus of lipopolysaccharide (2 ng/kg) to induce endotoxemia. Patients with sepsis, or controls with critical illness unrelated to sepsis, were recruited from four intensive care units.
RESULTS
Contact with endothelium and stimulation with lipopolysaccharide reduced the proportion of intermediate monocytes. Lipopolysaccharide increased tissue factor surface expression on classical and non-classical monocytes. Endotoxemia induced profound, transient monocytopenia, along with activation of coagulation pathways. In the remaining circulating monocytes, tissue factor was up-regulated in intermediate monocytes, though approximately 60 % of individuals (responders) up-regulated tissue factor across all monocyte subsets. In critically ill patients, tissue factor expression on intermediate and non-classical monocytes was significantly higher in patients with established sepsis than among non-septic patients. Upon recovery of sepsis, expression of tissue factor increased significantly in classical monocytes.
CONCLUSION
Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.
Topics: Humans; Monocytes; Endotoxemia; Thromboplastin; Thromboinflammation; Lipopolysaccharides; Sepsis
PubMed: 37263122
DOI: 10.1016/j.thromres.2023.05.018 -
Frontiers in Immunology 2024Exploring monocytes' roles within the tumor microenvironment is crucial for crafting targeted cancer treatments.
INTRODUCTION
Exploring monocytes' roles within the tumor microenvironment is crucial for crafting targeted cancer treatments.
METHODS
This study unveils a novel methodology utilizing four 20-color flow cytometry panels for comprehensive peripheral immune system phenotyping, specifically targeting classical, intermediate, and non-classical monocyte subsets.
RESULTS
By applying advanced dimensionality reduction techniques like t-distributed stochastic neighbor embedding (tSNE) and FlowSom analysis, we performed an extensive profiling of monocytes, assessing 50 unique cell surface markers related to a wide range of immunological functions, including activation, differentiation, and immune checkpoint regulation.
DISCUSSION
This in-depth approach significantly refines the identification of monocyte subsets, directly supporting the development of personalized immunotherapies and enhancing diagnostic precision. Our pioneering panel for monocyte phenotyping marks a substantial leap in understanding monocyte biology, with profound implications for the accuracy of disease diagnostics and the success of checkpoint-inhibitor therapies. Key findings include revealing distinct marker expression patterns linked to tumor progression and providing new avenues for targeted therapeutic interventions.
Topics: Humans; Monocytes; Flow Cytometry; Cluster Analysis; Biomarkers; Immunophenotyping; Tumor Microenvironment; Neoplasms
PubMed: 38742110
DOI: 10.3389/fimmu.2024.1405249 -
Cells Sep 2020Modulation of PARP1 expression, changes in its enzymatic activity, post-translational modifications, and inflammasome-dependent cleavage play an important role in the... (Review)
Review
The Role of PARP1 in Monocyte and Macrophage Commitment and Specification: Future Perspectives and Limitations for the Treatment of Monocyte and Macrophage Relevant Diseases with PARP Inhibitors.
Modulation of PARP1 expression, changes in its enzymatic activity, post-translational modifications, and inflammasome-dependent cleavage play an important role in the development of monocytes and numerous subtypes of highly specialized macrophages. Transcription of is governed by the proliferation status of cells at each step of their development. Higher abundance of PARP1 in embryonic stem cells and in hematopoietic precursors supports their self-renewal and pluri-/multipotency, whereas a low level of the enzyme in monocytes determines the pattern of surface receptors and signal transducers that are functionally linked to the NFκB pathway. In macrophages, the involvement of PARP1 in regulation of transcription, signaling, inflammasome activity, metabolism, and redox balance supports macrophage polarization towards the pro-inflammatory phenotype (M1), which drives host defense against pathogens. On the other hand, it seems to limit the development of a variety of subsets of anti-inflammatory myeloid effectors (M2), which help to remove tissue debris and achieve healing. PARP inhibitors, which prevent protein ADP-ribosylation, and PARP1‒DNA traps, which capture the enzyme on chromatin, may allow us to modulate immune responses and the development of particular cell types. They can be also effective in the treatment of monocytic leukemia and other cancers by reverting the anti- to the proinflammatory phenotype in tumor-associated macrophages.
Topics: Cell Differentiation; Humans; Macrophages; Monocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors
PubMed: 32900001
DOI: 10.3390/cells9092040 -
Journal of Biomechanics Feb 2017The role of cholesterol content on monocyte biomechanics remains understudied despite the well-established link between cholesterol and monocytes/macrophages in...
The role of cholesterol content on monocyte biomechanics remains understudied despite the well-established link between cholesterol and monocytes/macrophages in atherosclerosis, and the effect on other cell types. In this work, we have investigated the effect of cholesterol on monocyte deformability and the underlying molecular mechanisms. We altered the baseline cholesterol in human monocytic cell line THP-1, and investigated the changes in monocyte deformability using a custom microfluidic platform and atomic force microscopy. We observed that the cholesterol depletion lowered deformability while enrichment increased deformability compared to untreated cells. As a consequence of altered deformability, cholesterol depleted cells spread more on collagen-coated surfaces with elongated morphology, whereas cholesterol enriched cells had a more rounded morphology. We observed that the decreased deformability in cholesterol depleted cells, despite an increase in the fluidity of the membrane, is due to an increase in phosphorylation of Protein Kinase C (PKC), which translates to a higher degree of actin polymerization. Together, our results highlight the importance of biophysical regulation of monocyte response to cholesterol levels.
Topics: Biomechanical Phenomena; Cholesterol; Humans; Mechanical Phenomena; Membrane Fluidity; Monocytes; Phosphorylation; Protein Kinase C
PubMed: 28082022
DOI: 10.1016/j.jbiomech.2016.12.033 -
Revista Espanola de Quimioterapia :... Apr 2022Sepsis is one of the main causes of mortality in the emergency department (ED), due to the fact that signs and symptoms are common to other acute diseases, and this can... (Review)
Review
Sepsis is one of the main causes of mortality in the emergency department (ED), due to the fact that signs and symptoms are common to other acute diseases, and this can result in delayed detection. This diagnostic complexity has a huge impact on an entity in which early recognition determined treatment, as wells as enhance the patient's prognosis. Therefore, it is crucial to improve early identification. Different analytical tools arise from this approach, such as biomarkers: procalcitonin, C-reactive protein or MR-proadrenomedullin. In this review we will focus on a newer biomarker, the monocyte distribution width. The main objectives are to evaluate the usefulness of monocyte distribution width (MDW) in sepsis identification in ED, its limitations, and to compare it with other biomarker.
Topics: Biomarkers; C-Reactive Protein; Humans; Monocytes; Procalcitonin; Sepsis
PubMed: 35488816
DOI: 10.37201/req/s01.01.2022 -
Journal of Molecular and Cellular... Apr 2022Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury and dysfunction. Stabilin-1 is a scavenger receptor that regulates...
Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury and dysfunction. Stabilin-1 is a scavenger receptor that regulates several aspects of the innate immunity. Whether stabilin-1 affects the inflammatory response during viral myocarditis (VM) is entirely unknown. Here, we assess the role of stabilin-1 in the pathogenesis of VM and its suitability as a therapeutic target. Genetic loss of stabilin-1 increased mortality and cardiac necrosis in a mouse model of human Coxsackievirus B3 (CVB3)-induced myocarditis. Absence of stabilin-1 significantly reduced monocyte recruitment and strongly reduced the number of alternatively activated anti-inflammatory macrophages in the heart, enhancing a pro-inflammatory cardiac niche with a detrimental T lymphocyte response during VM. Yeast two-hybrid screening, confirmed by affinity chromatography, identified fibronectin as a stabilin-1 interacting partner. Absence of stabilin-1 specifically decreased monocyte adhesion on extracellular fibronectin in vitro. Loss of Type III repeats Extra Domain A (EDA) of fibronectin during VM also increased the mortality and cardiac necrosis as in stabilin-1 knockout mice, with reduced monocytic cardiac recruitment and increased T lymphocyte response. Collectively, stabilin-1 has an immune-suppressive role of limiting myocardial damage during VM, regulating anti-inflammatory monocyte-recruitment to the site of inflammation.
Topics: Animals; Cell Adhesion Molecules, Neuronal; Coxsackievirus Infections; Disease Models, Animal; Enterovirus B, Human; Fibronectins; Macrophages; Mice; Monocytes; Myocarditis; Necrosis; Virus Diseases
PubMed: 34968453
DOI: 10.1016/j.yjmcc.2021.12.009 -
Experimental Biology and Medicine... Jun 2021Bacteriophages are present in fluids from cirrhosis patients. However, their effect on the immune response is unknown. In this work, we explore the role of phages in the...
Bacteriophages are present in fluids from cirrhosis patients. However, their effect on the immune response is unknown. In this work, we explore the role of phages in the phenotype, function, and cytokine production of monocytes. We stimulated healthy monocytes with five different butanol-purified phage suspensions infective for Gram-negative and Gram-positive bacteria. We studied the expression of the monocyte markers involved in lipopolysaccharide recognition (LPS; CD14), antigen presentation (HLA-DR) and co-stimulation (CD86), and the concentration of induced cytokines (TNF-α, IFN-α, and IL-10) by phages. To confirm the direct role of phages without the interference of contaminating soluble LPS in phage suspensions, polymyxin B was added to the cell cultures. Phagocytosis experiments were assessed by flow cytometry using labeled phage suspensions. We observed that butanol-purified phages reduced the surface levels of CD14 and CD86 in monocytes and increased the secreted levels of TNF-α and IL-10 compared with the control sample containing only butanol buffer. All phage suspensions showed downregulation of HLA-DR expression but only phage contaminated with reached statistical significance. The addition of polymyxin B did not restore the monocytic response induced by phages, suggesting that the effect was not caused by the presence of LPS. Monocytes were able to phagocyte phages in a dose- and time-dependent manner. To conclude, the phagocytosis of butanol-purified phages altered the phenotype and cytokine production of monocytes suggesting they become tolerogenic.
Topics: Bacteriophages; Biomarkers; Butanols; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-10; Lipopolysaccharide Receptors; Lipopolysaccharides; Monocytes; Neutrophils; Phagocytosis; Polymyxin B; Tumor Necrosis Factor-alpha
PubMed: 33641443
DOI: 10.1177/1535370221995154 -
Journal of Thrombosis and Haemostasis :... Jul 2009Monocytes are the primary inflammatory cell type that infiltrates early atherosclerotic plaques. Their recruitment into plaques drives disease progression. Disease... (Review)
Review
Monocytes are the primary inflammatory cell type that infiltrates early atherosclerotic plaques. Their recruitment into plaques drives disease progression. Disease interventions that target monocytes could act at several points: alteration in the phenotype of circulating monocyte subpopulations; reduced recruitment of monocytes into plaques; alterations in the survival of monocyte-derived cells in atherosclerosis; and promotion of migratory egress from plaques to bring about resolution of the plaque inflammatory response. All of these points of intervention will be briefly discussed in this article.
Topics: Atherosclerosis; Chemotaxis, Leukocyte; Humans; Inflammation; Monocytes
PubMed: 19630762
DOI: 10.1111/j.1538-7836.2009.03423.x -
PloS One 2012Both nonclassical and intermediate monocytes have been implicated in different inflammatory conditions. We hypothesized that these monocytes would increase during...
INTRODUCTION
Both nonclassical and intermediate monocytes have been implicated in different inflammatory conditions. We hypothesized that these monocytes would increase during pregnancy, a condition associated with generalized activation of inflammatory responses and that they would increase even more during preeclampsia, in which inflammatory responses are further stimulated. In the present study we investigated changes in monocyte subsets during healthy pregnancy and preeclampsia in humans and rats.
METHODS
Blood monocyte subsets of nonpregnant, preeclamptic and healthy pregnant women were identified with CD14 and CD16. In nonpregnant and pregnant rats, blood monocytes were identified with CD172a and CD43, as well as in rats infused with adenosine triphosphate (ATP), a pro-inflammatory stimulus known to induce preeclampsia-like symptoms. Total and CD206-positive macrophages were quantified in placentas of these animals.
RESULTS
Lower percentages of classical monocytes were found in pregnant women (91%-[83-98%]) compared to nonpregnant women (94%-[90-98%]) and even less in preeclamptic patients (90%-[61-92%]). In contrast, the percentage of combined nonclassical/intermediate monocytes was higher in pregnant women (8.5%-[2.3-16.6%] vs. 5.6%-[1.9-9.5%]) and even higher in preeclamptic patients (9.9%-[7.8-38.7%]), which was caused by a selective increase of intermediate monocytes. In rats, we also found lower percentages of classical monocytes and higher percentages of nonclassical monocytes in pregnant versus nonpregnant rats. ATP infusion increased the percentage of nonclassical monocytes in pregnant rats even further but not in nonpregnant rats. These nonclassical monocytes showed a more activated phenotype in pregnant ATP-infused rats only. Mesometrial triangles of ATP-infused rats had less CD206-positive macrophages as compared to those of saline-infused rats.
CONCLUSION
The higher percentage of nonclassical/intermediate monocytes found in pregnancy and preeclampsia confirms their association with inflammatory responses. The observation that ATP stimulated numbers/activation of nonclassical monocytes in pregnant rats only, suggests that nonclassical monocytes are specifically altered in pregnancy and may play a role in the pathophysiology of preeclampsia.
Topics: Adenosine Triphosphate; Adult; Animals; Antigens, CD; Female; Flow Cytometry; Humans; Leukocyte Count; Monocytes; Placenta; Pre-Eclampsia; Pregnancy; Rats
PubMed: 23028864
DOI: 10.1371/journal.pone.0045229