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Siew Cheng Wong - One of the best experts on this subject based on the ideXlab platform.
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Image_2_Monocyte Subsets Have Distinct Patterns of Tetraspanin Expression and Different Capacities to Form Multinucleate Giant Cells.tif
2018Co-Authors: Thomas C. Champion, Siew Cheng Wong, Lynda J. Partridge, Siew-min Ong, Benoit Malleret, Peter N. MonkAbstract:Monocytes are able to undergo homotypic fusion to produce different types of multinucleated giant cells, such as Langhans giant cells in response to M. tuberculosis infection or foreign body giant cells in response to implanted biomaterials. Monocyte fusion is highly coordinated and complex, with various soluble, intracellular, and cell-surface components mediating different stages of the process. Tetraspanins, such as CD9, CD63, and CD81, are known to be involved in cell:cell fusion and have been suggested to play a role in regulating homotypic monocyte fusion. However, peripheral human Monocytes are not homogenous: they exist as a heterogeneous population consisting of three subsets, classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16+), at steady state. During infection with mycobacteria, the circulating populations of intermediate and non-classical Monocytes increase, suggesting they may play a role in the disease outcome. Human Monocytes were separated into subsets and then induced to fuse using concanavalin A. The intermediate Monocytes were able to fuse faster and form significantly larger giant cells than the other subsets. When antibodies targeting tetraspanins were added, the intermediate Monocytes responded to anti-CD63 by forming smaller giant cells, suggesting an involvement of tetraspanins in fusion for at least this subset. However, the expression of fusion-associated tetraspanins on monocyte subsets did not correlate with the extent of fusion or with the inhibition by tetraspanin antibody. We also identified a CD9High and a CD9Low monocyte population within the classical subset. The CD9High classical Monocytes expressed higher levels of tetraspanin CD151 compared to CD9Low classical Monocytes but the CD9High classical subset did not exhibit greater potential to fuse and the role of these cells in immunity remains unknown. With the exception of dendrocyte-expressed seven transmembrane protein, which was expressed at higher levels on the intermediate monocyte subset, the expression of fusion-related proteins between the subsets did not clearly correlate with their ability to fuse. We also did not observe any clear correlation between giant cell formation and the expression of pro-inflammatory or fusogenic cytokines. Although tetraspanin expression appears to be important for the fusion of intermediate Monocytes, the control of multinucleate giant cell formation remains obscure.
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Table_1_Monocyte Subsets Have Distinct Patterns of Tetraspanin Expression and Different Capacities to Form Multinucleate Giant Cells.docx
2018Co-Authors: Thomas C. Champion, Siew Cheng Wong, Lynda J. Partridge, Siew-min Ong, Benoit Malleret, Peter N. MonkAbstract:Monocytes are able to undergo homotypic fusion to produce different types of multinucleated giant cells, such as Langhans giant cells in response to M. tuberculosis infection or foreign body giant cells in response to implanted biomaterials. Monocyte fusion is highly coordinated and complex, with various soluble, intracellular, and cell-surface components mediating different stages of the process. Tetraspanins, such as CD9, CD63, and CD81, are known to be involved in cell:cell fusion and have been suggested to play a role in regulating homotypic monocyte fusion. However, peripheral human Monocytes are not homogenous: they exist as a heterogeneous population consisting of three subsets, classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16+), at steady state. During infection with mycobacteria, the circulating populations of intermediate and non-classical Monocytes increase, suggesting they may play a role in the disease outcome. Human Monocytes were separated into subsets and then induced to fuse using concanavalin A. The intermediate Monocytes were able to fuse faster and form significantly larger giant cells than the other subsets. When antibodies targeting tetraspanins were added, the intermediate Monocytes responded to anti-CD63 by forming smaller giant cells, suggesting an involvement of tetraspanins in fusion for at least this subset. However, the expression of fusion-associated tetraspanins on monocyte subsets did not correlate with the extent of fusion or with the inhibition by tetraspanin antibody. We also identified a CD9High and a CD9Low monocyte population within the classical subset. The CD9High classical Monocytes expressed higher levels of tetraspanin CD151 compared to CD9Low classical Monocytes but the CD9High classical subset did not exhibit greater potential to fuse and the role of these cells in immunity remains unknown. With the exception of dendrocyte-expressed seven transmembrane protein, which was expressed at higher levels on the intermediate monocyte subset, the expression of fusion-related proteins between the subsets did not clearly correlate with their ability to fuse. We also did not observe any clear correlation between giant cell formation and the expression of pro-inflammatory or fusogenic cytokines. Although tetraspanin expression appears to be important for the fusion of intermediate Monocytes, the control of multinucleate giant cell formation remains obscure.
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Monocyte Subsets Have Distinct Patterns of Tetraspanin Expression and Different Capacities to Form Multinucleate Giant Cells
Frontiers Media S.A., 2018Co-Authors: Siew Cheng Wong, Thomas C. Champion, Lynda J. Partridge, Siew-min Ong, Benoit Malleret, Peter N. MonkAbstract:Monocytes are able to undergo homotypic fusion to produce different types of multinucleated giant cells, such as Langhans giant cells in response to M. tuberculosis infection or foreign body giant cells in response to implanted biomaterials. Monocyte fusion is highly coordinated and complex, with various soluble, intracellular, and cell-surface components mediating different stages of the process. Tetraspanins, such as CD9, CD63, and CD81, are known to be involved in cell:cell fusion and have been suggested to play a role in regulating homotypic monocyte fusion. However, peripheral human Monocytes are not homogenous: they exist as a heterogeneous population consisting of three subsets, classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16+), at steady state. During infection with mycobacteria, the circulating populations of intermediate and non-classical Monocytes increase, suggesting they may play a role in the disease outcome. Human Monocytes were separated into subsets and then induced to fuse using concanavalin A. The intermediate Monocytes were able to fuse faster and form significantly larger giant cells than the other subsets. When antibodies targeting tetraspanins were added, the intermediate Monocytes responded to anti-CD63 by forming smaller giant cells, suggesting an involvement of tetraspanins in fusion for at least this subset. However, the expression of fusion-associated tetraspanins on monocyte subsets did not correlate with the extent of fusion or with the inhibition by tetraspanin antibody. We also identified a CD9High and a CD9Low monocyte population within the classical subset. The CD9High classical Monocytes expressed higher levels of tetraspanin CD151 compared to CD9Low classical Monocytes but the CD9High classical subset did not exhibit greater potential to fuse and the role of these cells in immunity remains unknown. With the exception of dendrocyte-expressed seven transmembrane protein, which was expressed at higher levels on the intermediate monocyte subset, the expression of fusion-related proteins between the subsets did not clearly correlate with their ability to fuse. We also did not observe any clear correlation between giant cell formation and the expression of pro-inflammatory or fusogenic cytokines. Although tetraspanin expression appears to be important for the fusion of intermediate Monocytes, the control of multinucleate giant cell formation remains obscure
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susceptibility and response of human blood monocyte subsets to primary dengue virus infection
PLOS ONE, 2012Co-Authors: Kok Loon Wong, Weiqiang Chen, Thavamalar Balakrishnan, Ying Xiu Toh, Katjia Fink, Siew Cheng WongAbstract:Human blood Monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood Monocytes are heterogeneous and divided into CD16− and CD16+ subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16− and CD16+ blood monocyte subsets to primary dengue virus in vitro. We found that both monocyte subsets were equally susceptible to dengue virus (DENV2 NGC), and capable of supporting the initial production of new infective virus particles. Both monocyte subsets produced anti-viral factors, including IFN-α, CXCL10 and TRAIL. However, CD16+ Monocytes were the major producers of inflammatory cytokines and chemokines in response to dengue virus, including IL-1β, TNF-α, IL-6, CCL2, 3 and 4. The susceptibility of both monocyte subsets to infection was increased after IL-4 treatment, but this increase was more profound for the CD16+ monocyte subset, particularly at early time points after virus exposure. These findings reveal the differential role that monocyte subsets might play during dengue disease.
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gene expression profiling reveals the defining features of the classical intermediate and nonclassical human monocyte subsets
Blood, 2011Co-Authors: Kok Loon Wong, Wingcheong Wong, Weihseun Yeap, Philippe Kourilsky, Siew Cheng WongAbstract:New official nomenclature subdivides human Monocytes into 3 subsets: the classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) Monocytes. This introduces new challenges, as monocyte heterogeneity is mostly understood based on 2 subsets, the CD16− and CD16+ Monocytes. Here, we comprehensively defined the 3 circulating human monocyte subsets using microarray, flow cytometry, and cytokine production analysis. We find that intermediate Monocytes expressed a large majority (87%) of genes and surface proteins at levels between classical and nonclassical Monocytes. This establishes their intermediary nature at the molecular level. We unveil the close relationship between the intermediate and nonclassic Monocytes, along with features that separate them. Intermediate Monocytes expressed highest levels of major histocompatibility complex class II, GFRα2 and CLEC10A, whereas nonclassic Monocytes were distinguished by cytoskeleton rearrangement genes, inflammatory cytokine production, and CD294 and Siglec10 surface expression. In addition, we identify new features for classic Monocytes, including AP-1 transcription factor genes, CLEC4D and IL-13Rα1 surface expression. We also find circumstantial evidence supporting the developmental relationship between the 3 subsets, including gradual changes in maturation genes and surface markers. By comprehensively defining the 3 monocyte subsets during healthy conditions, we facilitate target identification and detailed analyses of aberrations that may occur to monocyte subsets during diseases.
Maciej Siedlar - One of the best experts on this subject based on the ideXlab platform.
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reprint of alterations of trim21 mrna expression during monocyte maturation
Immunobiology, 2017Co-Authors: Marzena Lenart, Rafal Szatanek, Kazimierz Weglarczyk, Malgorzata Stec, Karolina Bukowskastrakova, Jaroslaw Czyz, Magdalena Rutkowskazapala, Anna Gruca, Maciej SiedlarAbstract:Abstract Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16+ monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) Monocytes, as well as during in vitro differentiation of the isolated Monocytes towards dendritic cells or macrophages. Our results revealed that the level of TRIM21 mRNA expression was significantly lower in CD16- Monocytes, when compared to CD16+ cells and the whole monocyte population, yet no significant differences were observed when CD16+ population was divided into intermediate and non-classical subsets. More pronounced differences were observed in the case of monocyte-derived macrophages (MDM) and dendritic cells (DCs). TRIM21-mRNA expression level was app. 6-fold higher in DCs, and app. 16-fold higher in MDM (p Our results may suggest the new mechanism of increased proinflammatory cytokine production by CD16+ (intermediate and non-classical) Monocytes and macrophages, at least in patients with acute or chronic infections, caused by enveloped viruses. We suggest that TRIM21 may be one of the factors associated with the “switching on” the proinflammatory programme in CD16+ Monocytes or monocyte-derived macrophages.
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alterations of trim21 mrna expression during monocyte maturation
Immunobiology, 2017Co-Authors: Marzena Lenart, Rafal Szatanek, Kazimierz Weglarczyk, Malgorzata Stec, Karolina Bukowskastrakova, Jaroslaw Czyz, Magdalena Rutkowskazapala, Anna Gruca, Maciej SiedlarAbstract:Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16+ monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) Monocytes, as well as during in vitro differentiation of the isolated Monocytes towards dendritic cells or macrophages. Our results revealed that the level of TRIM21 mRNA expression was significantly lower in CD16- Monocytes, when compared to CD16+ cells and the whole monocyte population, yet no significant differences were observed when CD16+ population was divided into intermediate and non-classical subsets. More pronounced differences were observed in the case of monocyte-derived macrophages (MDM) and dendritic cells (DCs). TRIM21-mRNA expression level was app. 6-fold higher in DCs, and app. 16-fold higher in MDM (p < 0,01), when compared to freshly isolated Monocytes. Our results may suggest the new mechanism of increased proinflammatory cytokine production by CD16+ (intermediate and non-classical) Monocytes and macrophages, at least in patients with acute or chronic infections, caused by enveloped viruses. We suggest that TRIM21 may be one of the factors associated with the “switching on” the proinflammatory programme in CD16+ Monocytes or monocyte-derived macrophages.
Catherine C. Hedrick - One of the best experts on this subject based on the ideXlab platform.
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Human Blood Monocyte Subsets: A New Gating Strategy Defined Using Cell Surface Markers Identified by Mass Cytometry.
Arteriosclerosis thrombosis and vascular biology, 2017Co-Authors: Graham D Thomas, Anouk A J Hamers, Paola Marcovecchio, Catherine Nakao, Chantel Mcskimming, Angela M Taylor, Anh T Nguyen, Coleen A. Mcnamara, Catherine C. HedrickAbstract:Objective— Human monocyte subsets are defined as classical (CD14 ++ CD16 − ), intermediate (CD14 ++ CD16 + ), and nonclassical (CD14 + CD16 + ). Alterations in monocyte subset frequencies are associated with clinical outcomes, including cardiovascular disease, in which circulating intermediate Monocytes independently predict cardiovascular events. However, delineating mechanisms of monocyte function is hampered by inconsistent results among studies. Approach and Results— We use cytometry by time-of-flight mass cytometry to profile human Monocytes using a panel of 36 cell surface markers. Using the dimensionality reduction approach visual interactive stochastic neighbor embedding, we define Monocytes by incorporating all cell surface markers simultaneously. Using visual interactive stochastic neighbor embedding, we find that although classical Monocytes are defined with high purity using CD14 and CD16, intermediate and nonclassical Monocytes defined using CD14 and CD16 alone are frequently contaminated, with average intermediate and nonclassical monocyte purity of ≈86.0% and 87.2%, respectively. To improve the monocyte purity, we devised a new gating scheme that takes advantage of the shared coexpression of cell surface markers on each subset. In addition to CD14 and CD16, CCR2, CD36, HLA-DR, and CD11c are the most informative markers that discriminate among the 3 monocyte populations. Using these additional markers as filters, our revised gating scheme increases the purity of both intermediate and nonclassical monocyte subsets to 98.8% and 99.1%, respectively. We demonstrate the use of this new gating scheme using conventional flow cytometry of peripheral blood mononuclear cells from subjects with cardiovascular disease. Conclusions— Using cytometry by time-of-flight mass cytometry, we have identified a small panel of surface markers that can significantly improve monocyte subset identification and purity in flow cytometry. Such a revised gating scheme will be useful for clinical studies of monocyte function in human cardiovascular disease.
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the transcription factor nr4a1 nur77 controls bone marrow differentiation and the survival of ly6c Monocytes
Nature Immunology, 2011Co-Authors: Richard N Hanna, Leo M Carlin, Harper Hubbeling, Dominika Nackiewicz, Angela M Green, Jennifer A Punt, Frederic Geissmann, Catherine C. HedrickAbstract:The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C- Monocytes. Ly6C- Monocytes, which function in a surveillance role in circulation, were absent from Nr4a1-/- mice. Normal numbers of myeloid progenitor cells were present in Nr4a1-/- mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from Nr4a1-/- mice developed fewer patrolling Monocytes than did recipients of wild-type bone marrow. The Ly6C- Monocytes remaining in the bone marrow of Nr4a1-/- mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C- Monocytes.
Frank Tacke - One of the best experts on this subject based on the ideXlab platform.
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hepatic recruitment of the inflammatory gr1 monocyte subset upon liver injury promotes hepatic fibrosis
Hepatology, 2009Co-Authors: K R Karlmark, Ralf Weiskirchen, Henning W Zimmermann, Nikolaus Gassler, Tom Luedde, Christian Trautwein, Christian Weber, Miriam Merad, Florent Ginhoux, Frank TackeAbstract:In addition to liver-resident Kupffer cells, infiltrating immune cells have recently been linked to the development of liver fibrosis. Blood Monocytes are circulating precursors of tissue macrophages and can be divided into two functionally distinct subpopulations in mice: Gr1hi (Ly6Chi) and Gr1lo (Ly6Clo) Monocytes. The role of these monocyte subsets in hepatic fibrosis and the mechanisms of their differential recruitment into the injured liver are unknown. We therefore characterized subpopulations of infiltrating Monocytes in acute and chronic carbon tetrachloride (CCl4)-induced liver injury in mice using flow cytometry and immunohistochemistry. Inflammatory Gr1hi but not Gr1lo Monocytes are massively recruited into the liver upon toxic injury constituting an up to 10-fold increase in CD11b+F4/80+ intrahepatic macrophages. Comparing wild-type with C-C chemokine receptor (CCR2)-deficient and CCR2/CCR6–deficient mice revealed that CCR2 critically controls intrahepatic Gr1hi monocyte accumulation by mediating their egress from bone marrow. During chronic liver damage, intrahepatic CD11b+F4/80+Gr1+ monocyte-derived cells differentiate preferentially into inducible nitric oxide synthase–producing macrophages exerting proinflammatory and profibrogenic actions, such as promoting hepatic stellate cell (HSC) activation, T helper 1–T cell differentiation and transforming growth factor β (TGF-β) release. Impaired monocyte subset recruitment in Ccr2−/− and Ccr2−/−Ccr6−/− mice results in reduced HSC activation and diminished liver fibrosis. Moreover, adoptively transferred Gr1hi Monocytes traffic into the injured liver and promote fibrosis progression in wild-type and Ccr2−/−Ccr6−/− mice, which are otherwise protected from hepatic fibrosis. Intrahepatic CD11b+F4/80+Gr1+ monocyte-derived macrophages purified from CCl4-treated animals, but not naive bone marrow Monocytes or control lymphocytes, directly activate HSCs in a TGF-β–dependent manner in vitro. Conclusion: Inflammatory Gr1+ Monocytes, recruited into the injured liver via CCR2-dependent bone marrow egress, promote the progression of liver fibrosis. Thus, they may represent an interesting novel target for antifibrotic strategies. (HEPATOLOGY 2009;50:261–274.)
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monocyte subsets differentially employ ccr2 ccr5 and cx3cr1 to accumulate within atherosclerotic plaques
Journal of Clinical Investigation, 2007Co-Authors: Frank Tacke, Alexandre Garin, David Alvarez, Theodore J Kaplan, Claudia Jakubzick, Rainer Spanbroek, Nico Van Rooijen, Matthias Mack, Jaime Llodra, Sergio A LiraAbstract:Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2+CX3CR1+Ly-6Chi and CCR2–CX3CR1++Ly-6Clo Monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE-deficient mice and traced their differentiation and chemokine receptor usage as they accumulated within atherosclerotic plaques. Blood monocyte counts were elevated in apoE–/– mice and skewed toward an increased frequency of CCR2+Ly-6Chi Monocytes in apoE–/– mice fed a high-fat diet. CCR2+Ly-6Chi Monocytes efficiently accumulated in plaques, whereas CCR2–Ly-6Clo Monocytes entered less frequently but were more prone to developing into plaque cells expressing the dendritic cell–associated marker CD11c, indicating that phagocyte heterogeneity in plaques is linked to distinct types of entering Monocytes. CCR2– Monocytes did not rely on CX3CR1 to enter plaques. Instead, they were partially dependent upon CCR5, which they selectively upregulated in apoE–/– mice. By comparison, CCR2+Ly-6Chi Monocytes unexpectedly required CX3CR1 in addition to CCR2 and CCR5 to accumulate within plaques. In many other inflammatory settings, these Monocytes utilize CCR2, but not CX3CR1, for trafficking. Thus, antagonizing CX3CR1 may be effective therapeutically in ameliorating CCR2+ monocyte recruitment to plaques without impairing their CCR2-dependent responses to inflammation overall.
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monocyte subsets differentially employ ccr2 ccr5 and cx3cr1 to accumulate within atherosclerotic plaques
Journal of Clinical Investigation, 2007Co-Authors: Frank Tacke, Alexandre Garin, David Alvarez, Theodore J Kaplan, Claudia Jakubzick, Rainer Spanbroek, Nico Van Rooijen, Matthias Mack, Jaime Llodra, Sergio A LiraAbstract:Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2+CX3CR1+Ly-6Chi and CCR2–CX3CR1++Ly-6Clo Monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE-deficient mice and traced their differentiation and chemokine receptor usage as they accumulated within atherosclerotic plaques. Blood monocyte counts were elevated in apoE–/– mice and skewed toward an increased frequency of CCR2+Ly-6Chi Monocytes in apoE–/– mice fed a high-fat diet. CCR2+Ly-6Chi Monocytes efficiently accumulated in plaques, whereas CCR2–Ly-6Clo Monocytes entered less frequently but were more prone to developing into plaque cells expressing the dendritic cell–associated marker CD11c, indicating that phagocyte heterogeneity in plaques is linked to distinct types of entering Monocytes. CCR2– Monocytes did not rely on CX3CR1 to enter plaques. Instead, they were partially dependent upon CCR5, which they selectively upregulated in apoE–/– mice. By comparison, CCR2+Ly-6Chi Monocytes unexpectedly required CX3CR1 in addition to CCR2 and CCR5 to accumulate within plaques. In many other inflammatory settings, these Monocytes utilize CCR2, but not CX3CR1, for trafficking. Thus, antagonizing CX3CR1 may be effective therapeutically in ameliorating CCR2+ monocyte recruitment to plaques without impairing their CCR2-dependent responses to inflammation overall.
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migratory fate and differentiation of blood monocyte subsets
Immunobiology, 2006Co-Authors: Frank Tacke, Gwendalyn J RandolphAbstract:Abstract Monocytes are established circulating precursors for tissue macrophages and dendritic cells (DCs). Monocyte-derived macrophages and DCs fulfill critical roles in innate and adaptive immunity during inflammation, and it is believed that Monocytes also maintain these populations in peripheral tissues during homeostasis. However, the continuous replenishment of any DC pool by blood Monocytes in the steady state remains to be established, and some macrophage populations may be self-renewing in the steady state. Recent identification of mouse monocyte subsets that closely resemble human monocyte subsets has inspired a variety of techniques wherein Monocytes can be readily traced in vivo to address these critical questions. There are two major monocyte subsets that vary in chemokine receptor (CCR) and adhesion molecule expression, and in migratory and differentiation properties. In humans, ‘classical’ CD14 + CD16 − Monocytes express CCR2, CD64, CD62L, whereas ‘non-classical’ CD14 low CD16 + Monocytes lack CCR2. Their counterparts in mice are CCR2 + Gr-1 hi and CCR2 − Gr-1 low Monocytes, respectively. Gr-1 hi (Ly6C hi ) Monocytes are recruited to inflammatory sites, e.g. inflamed skin or acutely inflamed peritoneum and give rise to macrophages and DCs in inflammatory or infectious disease models and to epidermal Langerhans cells after skin inflammation. Gr-1 low Monocytes have been proposed as precursors for steady state DCs, but experimental evidence is as of yet limited. Fortunately, the rate of progress in the study of monocyte fate is rapidly picking up pace, giving rise to the expectation that we will soon know much more about the biology of Monocytes in the steady state and inflammation.
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role of ccr8 and other chemokine pathways in the migration of monocyte derived dendritic cells to lymph nodes
Journal of Experimental Medicine, 2004Co-Authors: Chunfeng Qu, Emmerson W Edwards, Guzman Sanchezschmitz, Alexandre Garin, Véronique Angeli, Frank Tacke, Nasreen S Haque, Jaime Llodra, Wendy PetersAbstract:Studying the influence of chemokine receptors (CCRs) on monocyte fate may reveal information about which subpopulations of Monocytes convert to dendritic cells (DCs) and the migration pathways that they use. First, we examined whether prominent CCRs on different monocyte subsets, CCR2 or CX3CR1, mediated migration events upstream of the accumulation of monocyte-derived DCs in lymph nodes (LNs). Monocytes were labeled and traced by uptake of latex microspheres in skin. Unexpectedly, neither CCR2 nor CX3CR1 were required. However, absence of CCR2 led to an increased labeling of the minor Gr-1int monocyte population, and the number of latex+ DCs that emigrated to LNs was correspondingly increased. Characterization of Gr-1int Monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood. CCR7 and CCR8 pathways were used by monocyte-derived DCs during mobilization from skin to LNs. The role of CCR8 in emigration from tissues also applied to human monocyte-derived cells in a model of transendothelial trafficking. Collectively, the data suggest that Gr-1int Monocytes may be most disposed to become a lymphatic-migrating DCs. When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs.
Suzanne M Crowe - One of the best experts on this subject based on the ideXlab platform.
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glucose transporter 1 expressing proinflammatory Monocytes are elevated in combination antiretroviral therapy treated and untreated hiv subjects
Journal of Immunology, 2014Co-Authors: Clovis Princesteve Palmer, Anthony Jaworowski, Suzanne M Crowe, Joshua J Anzinger, Jingling Zhou, Maelenn Gouillou, Alan L Landay, Joseph M MccuneAbstract:Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated Monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV + ) treatment-naive individuals ( n = 17), HIV + individuals on combination antiretroviral therapy with viral loads below detection ( n = 11), and HIV-seronegative (HIV − ) individuals ( n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-( N -(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, Monocytes from HIV + persons had significantly increased surface expression of Glut1 compared with those from HIV − controls. Nonclassical (CD14 + CD16 ++ ) and intermediate (CD14 ++ CD16 + ) monocyte subpopulations showed higher Glut1 expression than did classical (CD14 ++ CD16 − ) Monocytes. Intermediate Monocytes from treatment-naive HIV + individuals also showed increased uptake of 2-( N -(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV − controls. Our results show that HIV infection is associated with increased glucose metabolism in Monocytes and that Glut1 expression by proinflammatory Monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.
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Differential expression of CD163 on monocyte subsets in healthy and HIV-1 infected individuals.
PLOS ONE, 2011Co-Authors: Emma Dawn Tippett, Wan-jung Cheng, Paul U. Cameron, Anthony Jaworowski, Bruce J Brew, Clare L V Westhorpe, Sharon R. Lewin, Suzanne M CroweAbstract:CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by Monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ Monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- Monocytes but not on CD14+CD16++ Monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ Monocytes to the same extent as CD14++CD16− Monocytes. CD163 expression on CD14++CD16+ Monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− Monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− Monocytes and induced in pro-inflammatory CD14+CD16++ Monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on Monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals.