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.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Monocytes are critical defense components that play an important role in the primary innate immune response. The heterogeneous nature of monocytes and their ability to differentiate into either ...monocyte-derived macrophages or monocyte-derived dendritic cells allows them to serve as a bridge between the innate and adaptive immune responses. Current studies of monocytes based on immunofluorescence, single-cell RNA sequencing and whole mass spectrometry finger printing reveals different classification systems for monocyte subsets. In humans, three circulating monocyte subsets are classified based on relative expression levels of CD14 and CD16 surface proteins, namely classical, intermediate and non-classical subsets. Transcriptomic analyses of these subsets help to define their distinct functional properties. Tuberculosis (TB) is a disease instigated by the deadly pathogen
. Current research on monocytes in TB has indicated that there are alterations in the frequency of intermediate and non-classical subsets suggesting their impact in bacterial persistence. In this review, we will focus on these monocyte subsets, including their classification, frequency distribution, cytokine profiles, role as a biomarker and will comment on future directions for understanding the salient phenotypic and functional properties relevant to TB pathogenesis.
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Monocyte‐derived macrophages (MDMs) generated from peripheral blood monocytes are widely used to model human macrophages for in vitro studies. However, the possible impact of different ...isolation methods on the resulting MDM phenotype is poorly described. We aimed to investigate the effects of three commonly used monocyte isolation techniques on the resulting MDM phenotype. Plastic adhesion, negative selection, and CD14pos selection were compared. Monocyte‐derived macrophages were generated by 5‐day culture with macrophage and granulocyte–macrophage colony‐stimulating factors. We investigated monocyte and MDM yields, purity, viability, and cell phenotype. CD14pos selection resulted in highest monocyte yield (19·8 × 106 cells, equivalent to 70% of total) and purity (98·7%), compared with negative selection (17·7 × 106 cells, 61% of total, 85·0% purity), and plastic adhesion (6·1 × 106 cells, 12·9% of total, 44·2% purity). Negatively selected monocytes were highly contaminated with platelets. Expression of CD163 and CD14 were significantly lower on CD14pos selection and plastic adhesion monocytes, compared with untouched peripheral blood mononuclear cells. After maturation, CD14pos selection also resulted in the highest MDM purity (98·2%) compared with negative selection (94·5%) and plastic adhesion (66·1%). Furthermore, MDMs from plastic adhesion were M1‐skewed (CD80high HLA‐DRhigh CD163low), whereas negative selection MDMs were M2‐skewed (CD80low HLA‐DRlow CD163high). Choice of monocyte isolation method not only significantly affects yield and purity, but also impacts resulting phenotype of cultured MDMs. These differences may partly be explained by the presence of contaminating cells when using plastic adherence or negative selection. Careful considerations of monocyte isolation methods are important for designing in vitro assays on MDMs.
Different monocyte‐isolation techniques affect both cell yield, and purity and phenotype of isolated monocytes and monocyte‐derived macrophages in vitro.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
•MCP-1 inculpated in the pathogenesis of numerous diseases either directly or indirectly.•Elevated level of MCP-1 has been observed in COVID-19 patients also.•MCP-1 has a vital role in the process of ...inflammation.•MCP-1 act through migration and infiltration of inflammatory cells and cytokines at the site of inflammation.•MCP-1 attracts or enhances the expression of other inflammatory factors/cells as well.
MCP-1 (Monocyte chemoattractant protein-1), also known as Chemokine (CC-motif) ligand 2 (CCL2), is from family of CC chemokines. It has a vital role in the process of inflammation, where it attracts or enhances the expression of other inflammatory factors/cells. It leads to the advancement of many disorders by this main mechanism of migration and infiltration of inflammatory cells like monocytes/macrophages and other cytokines at the site of inflammation. MCP-1 has been inculpated in the pathogenesis of numerous disease conditions either directly or indirectly like novel corona virus, cancers, neuroinflammatory diseases, rheumatoid arthritis, cardiovascular diseases. The elevated MCP-1 level has been observed in COVID-19 patients and proven to be a biomarker associated with the extremity of disease along with IP-10. This review will focus on involvement and role of MCP-1 in various pathological conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. Murine Ly6C+ monocytes display developmental plasticity and are recruited to ...complement tissue-resident macrophages and dendritic cells on demand. Murine vascular Ly6C− monocytes patrol the endothelium, act as scavengers, and support vessel wall repair. Here we characterized population and single cell transcriptomes, as well as enhancer and promoter landscapes of the murine monocyte compartment. Single cell RNA-seq and transplantation experiments confirmed homeostatic default differentiation of Ly6C+ into Ly6C− monocytes. The main two subsets were homogeneous, but linked by a more heterogeneous differentiation intermediate. We show that monocyte differentiation occurred through de novo enhancer establishment and activation of pre-established (poised) enhancers. Generation of Ly6C− monocytes involved induction of the transcription factor C/EBPβ and C/EBPβ-deficient mice lacked Ly6C− monocytes. Mechanistically, C/EBPβ bound the Nr4a1 promoter and controlled expression of this established monocyte survival factor.
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•Steady-state Ly6C+ and Ly6C− monocytes are homogeneous populations•Ly6Cint monocytes comprise a heterogeneous population expressing MHCII•C/EBPβ regulates monocyte differentiation from Ly6C+ into Ly6C− cells•Expression of the monocyte survival factor Nr4a1 is regulated by C/EBPβ
Monocytes are circulating, short-lived blood cells. Here, Mildner et al. (2017) use transcriptome and epigenome profiling to study murine monocyte identities and subset interrelations. They highlight the critical role of C/EBPβ in monocyte conversion and reveal that while Ly6C+ and Ly6C− monocytes are homogeneous in steady state, Ly6Cint cells display heterogeneity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
After entering tissues, monocytes differentiate into cells that share functional features with either macrophages or dendritic cells (DCs). How monocyte fate is directed toward monocyte-derived ...macrophages (mo-Macs) or monocyte-derived DCs (mo-DCs) and which transcription factors control these differentiation pathways remains unknown. Using an in vitro culture model yielding human mo-DCs and mo-Macs closely resembling those found in vivo in ascites, we show that IRF4 and MAFB were critical regulators of monocyte differentiation into mo-DCs and mo-Macs, respectively. Activation of the aryl hydrocarbon receptor (AHR) promoted mo-DC differentiation through the induction of BLIMP-1, while impairing differentiation into mo-Macs. AhR deficiency also impaired the in vivo differentiation of mouse mo-DCs. Finally, AHR activation correlated with mo-DC infiltration in leprosy lesions. These results establish that mo-DCs and mo-Macs are controlled by distinct transcription factors and show that AHR acts as a molecular switch for monocyte fate specification in response to micro-environmental factors.
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•IRF4 and MAFB are essential for human mo-DC and mo-Mac differentiation, respectively•AHR activation promotes mo-DC and inhibits mo-Mac differentiation through BLIMP-1•AhR is involved in the in vivo differentiation of mo-DCs in the mouse
How monocytes differentiate into dendritic cells versus macrophages is poorly understood. Goudot et al. show that IRF4 and MAFB are essential for dendritic cell or macrophage differentiation, respectively, and identify aryl hydrocarbon receptor as a major regulator of monocyte fate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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