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Immunity Oct 2018Novel experimental approaches such as fate-mapping and single-cell analysis have brought fresh insight into monocyte development and function over the past decade and... (Review)
Review
Novel experimental approaches such as fate-mapping and single-cell analysis have brought fresh insight into monocyte development and function over the past decade and helped redefine the monocyte field. Monocytes are now known to consist of multiple subsets generated through distinct developmental pathways with diverse functional specializations. Their fates under homeostatic conditions include the accumulation in peripheral reservoirs and the engraftment into certain resident macrophage pools. Under pathological conditions, monocytes acquire inflammatory effector functions, but can also develop regulatory properties essential for tissue repair. Importantly, monocytes recruited during inflammation are often functionally distinct from resident macrophages or conventional dendritic cells. Here we outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity and discuss how these bring new perspectives to monocyte research.
Topics: Animals; Cell Differentiation; Cell Movement; Dendritic Cells; Homeostasis; Humans; Inflammation; Macrophages; Models, Immunological; Monocytes
PubMed: 30332628
DOI: 10.1016/j.immuni.2018.10.005 -
International Immunopharmacology Nov 2014THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and... (Review)
Review
THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. This cell line has become a common model to estimate modulation of monocyte and macrophage activities. This review attempts to summarize and discuss recent publications related to the THP-1 cell model. An overview on the biological similarities and dissimilarities between the THP-1 cell line and human peripheral blood mononuclear cell (PBMC) derived-monocytes and macrophages, as well as the advantages and disadvantages of the use of THP-1 cell line, is included. The review summarizes different published co-cultivation studies of THP-1 cells with other cell types, for instance, intestinal cells, adipocytes, T-lymphocytes, platelets, and vascular smooth muscle cells, which can be an option to study cell-cell interaction in vitro and can be an approach to better mimic in vivo conditions. Macrophage polarization is a relatively new topic which gains interest for which the THP-1 cell line also may be relevant. Besides that an overview of newly released commercial THP-1 engineered-reporter cells and THP-1 inflammasome test-cells is also given. Evaluation of recent papers leads to the conclusion that the THP-1 cell line has unique characteristics as a model to investigate/estimate immune-modulating effects of compounds in both activated and resting conditions of the cells. Although the THP-1 response can hint to potential responses that might occur ex vivo or in vivo, these should be, however, validated by in vivo studies to draw more definite conclusions.
Topics: Cell Communication; Cell Differentiation; Cell Line, Tumor; Humans; Immunomodulation; Leukocytes, Mononuclear; Macrophages; Models, Biological; Monocytes
PubMed: 25130606
DOI: 10.1016/j.intimp.2014.08.002 -
Journal of Leukocyte Biology Aug 2019Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding... (Review)
Review
Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding of monocytes has advanced from viewing these cells as a homogenous population to a heterogeneous system of cells that display diverse responses to different stimuli. During cancer, different monocyte subsets perform functions that contribute to both pro- and antitumoral immunity, including phagocytosis, secretion of tumoricidal mediators, promotion of angiogenesis, remodeling of the extracellular matrix, recruitment of lymphocytes, and differentiation into tumor-associated macrophages and dendritic cells. The ability of cancer to evade immune recognition and clearance requires protumoral signals to outweigh ongoing attempts by the host immune system to prevent tumor growth. This review discusses current understanding of monocyte heterogeneity during homeostasis, highlights monocyte functions in cancer progression, and describes monocyte-targeted therapeutic strategies for cancer treatment.
Topics: Animals; Biomarkers; Cell Movement; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunophenotyping; Monocytes; Neoplasms; Tumor Microenvironment
PubMed: 30776148
DOI: 10.1002/JLB.4RI0818-311R -
Annual Review of Pathology Jan 2021Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a... (Review)
Review
Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various mechanisms that induce immune tolerance, angiogenesis, and increased dissemination of tumor cells. Yet monocytes can also give rise to antitumor effectors and activate antigen-presenting cells. This yin-yang activity relies on the plasticity of monocytes in response to environmental stimuli. In this review, we summarize current knowledge of the ontogeny, heterogeneity, and functions of monocytes and monocyte-derived cells in cancer, pinpointing the main pathways that are important for modeling the immunosuppressive tumor microenvironment.
Topics: Animals; Humans; Monocytes; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 33497262
DOI: 10.1146/annurev-pathmechdis-012418-013058 -
Arteriosclerosis, Thrombosis, and... Jan 2017Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There... (Review)
Review
Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There are 2 subsets of monocytes in mice (3 subsets in humans) that are mobilized from the bone marrow and recruited to sites of inflammation, where they carry out their respective functions in promoting inflammation or facilitating tissue repair. Our understanding of the fate of these monocyte subsets at the site of inflammation is constantly evolving. This brief review highlights the plasticity of monocyte subsets and their conversion during inflammation and injury.
Topics: Animals; Cell Plasticity; Chemotaxis, Leukocyte; Hemostasis; Humans; Inflammation; Inflammation Mediators; Macrophages; Mice; Monocytes; Phenotype; Signal Transduction; Wound Healing
PubMed: 27765768
DOI: 10.1161/ATVBAHA.116.308198 -
Frontiers in Immunology 2019Circulating monocytes can infiltrate mucosal or inflamed tissues where they differentiate into either macrophages or dendritic cells. This paradigm is supported by... (Review)
Review
Circulating monocytes can infiltrate mucosal or inflamed tissues where they differentiate into either macrophages or dendritic cells. This paradigm is supported by numerous studies conducted in mice and in different settings for human cells. Determining whether it holds true in humans is essential for the successful design of monocyte-targeting therapies. Despite limitations inherent to working with human samples, there is accumulating evidence of the existence of generated monocyte-derived cells in humans. Here, we review recent studies showing the recruitment of human monocytes into tissues and their differentiation into macrophages or dendritic cells, in normal or pathological settings. We examine the methods available in human studies to demonstrate the monocytic origin of infiltrating cells. Finally, we review the functions of human monocyte-derived cells and how they might contribute to pathogeny.
Topics: Animals; Dendritic Cells; Humans; Macrophages; Monocytes; Myelopoiesis
PubMed: 31456804
DOI: 10.3389/fimmu.2019.01907 -
Scandinavian Journal of Immunology Jul 2020Monocytes are important cells of the innate system. They are a heterogeneous type of cells consisting of phenotypically and functionally distinct subpopulations, which... (Review)
Review
Monocytes are important cells of the innate system. They are a heterogeneous type of cells consisting of phenotypically and functionally distinct subpopulations, which play a specific role in the control, development and escalation of the immunological processes. Based on the expression of superficial CD14 and CD16 in flow cytometry, they can be divided into three subsets: classical, intermediate and non-classical. Variation in the levels of human monocyte subsets in the blood can be observed in patients in numerous pathological states, such as infections, cardiovascular and inflammatory diseases, cancer and autoimmune diseases. The aim of this review is to summarize current knowledge of human monocyte subsets and their significance in homeostasis and in pathological conditions.
Topics: Colony-Stimulating Factors; Humans; Immunity, Innate; Macrophages; Monocytes; Receptors, Cell Surface
PubMed: 32243617
DOI: 10.1111/sji.12883 -
PloS One 2020The monocyte-derived dendritic cells (moDCs) are a subset of dendritic cells widely used in immunological studies as a convenient and easy approach after isolation of...
The monocyte-derived dendritic cells (moDCs) are a subset of dendritic cells widely used in immunological studies as a convenient and easy approach after isolation of mononuclear cells directly from peripheral blood mononuclear cells (PBMC). Both the purification and cell culture of monocytes impact on the differentiation of monocytes into moDCs. The methodology to isolate and differentiate monocytes into moDCs is still controversial. We aimed to compare three different protocols for monocyte isolation from PBMC: 1) Cold-aggregation; 2) Percoll gradient; and 3) Magnetic beads cell-enrichment. Additionally we also compared four different monocyte differentiation and culture techniques: 1) Cell culture media; 2) Serum sources; 3) required GM-CSF and IL-4 concentrations; 4) Cell culture systems. We used flow cytometry analysis of light scattering and/or expression of pan surface markers, such as CD3, CD14 and CD209 to determine isolation/differentiation degree. Purified PBMC followed by two steps of cold aggregation, yielded cell viability around 95% with poor monocyte enrichment (monocytes increase vs. lymphocytes reduction was not statistically significant, p>0.05). Conversely, monocyte isolation from PBMC with discontinuous Percoll gradient generated around 50% cell viability. Albeit, we observed a significant reduction (p≤0.05) of lymphocytes contaminants. The magnetic beads cell-enrichment yield cell viability higher than 95%, as high as a significant lymphocyte depletion (p≤0.005) when compared to all other techniques employed. The moDCs showed better differentiation based on increased CD209 expression, but lower CD14 levels, when cells were cultured in RPMI medium plus 500IU/mL of both GM-CSF and IL-4 in a semi-adherent fashion. Serum sources showed no influence on the culture performance. In conclusion, the magnetic beads cell-enrichment showed superior cell viability, indicating that this approach is a better choice to isolate monocytes, and moDCs cultured afterwards in appropriate medium, serum, cytokines and culture system might influence the monocytes differentiation into moDC.
Topics: Antigens, CD; Cell Differentiation; Cell Separation; Cell Survival; Cells, Cultured; Dendritic Cells; Flow Cytometry; Fluorescence; Humans; Monocytes; Scattering, Radiation
PubMed: 32271804
DOI: 10.1371/journal.pone.0231132 -
Cancer Discovery Apr 2018We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are...
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4 T cells and CD8 T-cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select Toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression. We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic. .
Topics: Animals; Bacteria; Carcinogenesis; Cell Differentiation; Female; Humans; Male; Mice; Microbiota; Monocytes; Pancreatic Neoplasms; Signal Transduction; Toll-Like Receptors
PubMed: 29567829
DOI: 10.1158/2159-8290.CD-17-1134 -
Cytometry. Part B, Clinical Cytometry May 2017In April 2013, a symposium was organized to highlight different aspects of differentiation and activation of the monocyte-macrophage lineage as analyzed on the flow...
In April 2013, a symposium was organized to highlight different aspects of differentiation and activation of the monocyte-macrophage lineage as analyzed on the flow cytometer. Characterization of this lineage requires knowledge of the maturation process from their progenitors that are present in bone marrow up to the mature monocytic cells in peripheral blood, because each monocytic lineage cell with an aberrant phenotype refers to the corresponding maturation stage. A standardized quantitative analysis will facilitate the monitoring of the pathological processes and the clinical features, such as the outcome of treatment. However, changes in marker expression by variation in intensity, asynchronism, and lineage infidelity must be considered. The dynamics of normal marker expressions in early differentiation stages, e.g. molecules like HLA II, CD64 or CD14, give rise to a hypothesis on their possible role in monocyte ontogeny. Besides their usual role in tissue homeostasis, mature macrophages may also play a similar role in hematopoiesis. This meeting highlighted the large potential of flow cytometric tools available for monitoring of all these aspects in the monocytic and macrophage cell lineage. © 2015 International Clinical Cytometry Society.
Topics: Cell Differentiation; Cell Lineage; Flow Cytometry; Humans; Macrophages; Monocytes
PubMed: 26332381
DOI: 10.1002/cyto.b.21280