Phenotype, function, and differentiation potential of human monocyte subsets
Autor: | Diana Metes, Geetha Chalasani, John T. Walters, Juan M. Taboas, Beth Elinoff, Bala Ramaswami, Fadi G. Lakkis, Kevin Hadi, Lisa B. Boyette, Camila Macedo |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Physiology Cellular differentiation Interleukin-1beta lcsh:Medicine Monocytes White Blood Cells 0302 clinical medicine Animal Cells Interferon Immune Physiology Medicine and Health Sciences Macrophage lcsh:Science Cells Cultured Staining Innate Immune System Multidisciplinary T Cells Toll-Like Receptors Cell Staining Cell Differentiation Phenotype medicine.anatomical_structure Cytokines Tumor necrosis factor alpha Cellular Types Research Article medicine.drug Imaging Techniques Immune Cells T cell CD14 Immunology Biology CD16 Research and Analysis Methods Immunophenotyping 03 medical and health sciences Phagocytosis Fluorescence Imaging medicine Humans Secretion Blood Cells Interleukin-6 Tumor Necrosis Factor-alpha Macrophage Colony-Stimulating Factor Macrophages lcsh:R Granulocyte-Macrophage Colony-Stimulating Factor Biology and Life Sciences Dendritic Cells Cell Biology Molecular Development 030104 developmental biology Microscopy Fluorescence Specimen Preparation and Treatment Immune System lcsh:Q Physiological Processes Developmental Biology 030215 immunology |
Zdroj: | PLoS ONE, Vol 12, Iss 4, p e0176460 (2017) PLoS ONE |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0176460 |
Popis: | Human monocytes have been grouped into classical (CD14++CD16−), non-classical (CD14dimCD16++), and intermediate (CD14++CD16+) subsets. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells (DC) or macrophages, remains incomplete. We therefore phenotyped monocytes from peripheral blood of healthy subjects and performed functional studies on high-speed sorted subsets. Subset frequencies were found to be tightly controlled over time and across individuals. Subsets were distinct in their secretion of TNFα, IL-6, and IL-1β in response to TLR agonists, with classical monocytes being the most producers and non-classical monocytes the least. Monocytes, particularly those of the non-classical subtype, secreted interferon-α (IFN-α) in response to intracellular TLR3 stimulation. After incubation with IL-4 and GM-CSF, classical monocytes acquired monocyte-derived DC (mo-DC) markers and morphology and stimulated allogeneic T cell proliferation in MLR; intermediate and non-classical monocytes did not. After incubation with IL-3 and Flt3 ligand, no subset differentiated to plasmacytoid DC. After incubation with GM-CSF (M1 induction) or macrophage colony-stimulating factor (M-CSF) (M2 induction), all subsets acquired macrophage morphology, secreted macrophage-associated cytokines, and displayed enhanced phagocytosis. From these studies we conclude that classical monocytes are the principal source of mo-DCs, but all subsets can differentiate to macrophages. We also found that monocytes, in particular the non-classical subset, represent an alternate source of type I IFN secretion in response to virus-associated TLR agonists. |
Databáze: | OpenAIRE |
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