Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products
Copyright policy )Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products
Abstract HIV infects activated CD4+ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)+ and CD1c (BDCA-1)+ dendritic cell counts were reduced. Conversely, CD14+CD16++ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14++CD16−M-DC8− monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8+ monocytes were mostly responsible for this overproduction. Moreover, M-DC8+ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8+ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression.
MESH: Monocytes/pathology, Lipopolysaccharides, Male, Thrombomodulin, MESH: Flow Cytometry, HIV Infections, MESH: Monocytes/drug effects, MESH: HIV Infections/pathology, Monocytes, MESH: Membrane Glycoproteins/antagonists & inhibitors, Antigens, CD1, MESH: Anti-HIV Agents/therapeutic use, Surface/metabolism, MESH: Monocytes/metabolism, Cells, Cultured, MESH: Up-Regulation*/drug effects, MESH: Dendritic Cells/metabolism, MESH: Cells, MESH: Middle Aged, Cultured, Membrane Glycoproteins, MESH: HIV Infections/drug therapy, MESH: Macrophages/immunology, Antibodies, Monoclonal, MESH: Viremia/drug therapy, MESH: Macrophages/drug effects, Middle Aged, Flow Cytometry, MESH: Young Adult, MESH: Dendritic Cells/immunology, Antigens, Surface, MESH: Dendritic Cells/drug effects, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Antigens, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Macrophage Activation/drug effects, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Anti-HIV Agents, MESH: Monocytes/immunology, MESH: Tumor Necrosis Factor-alpha/metabolism, MESH: Glycoproteins, MESH: Viremia/immunology, MESH: Lipopolysaccharides/toxicity, Humans, MESH: Macrophages/metabolism, Glycoproteins, MESH: Humans, CD1, MESH: Antibodies, Monoclonal/metabolism, Macrophages, MESH: HIV Infections/metabolism, MESH: Viremia/metabolism, MESH: Adult, MESH: HIV Infections/immunology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Dendritic Cells, Macrophage Activation, MESH: Male, MESH: Macrophages/pathology, MESH: Dendritic Cells/pathology Female, MESH: Viremia/pathology
MESH: Monocytes/pathology, Lipopolysaccharides, Male, Thrombomodulin, MESH: Flow Cytometry, HIV Infections, MESH: Monocytes/drug effects, MESH: HIV Infections/pathology, Monocytes, MESH: Membrane Glycoproteins/antagonists & inhibitors, Antigens, CD1, MESH: Anti-HIV Agents/therapeutic use, Surface/metabolism, MESH: Monocytes/metabolism, Cells, Cultured, MESH: Up-Regulation*/drug effects, MESH: Dendritic Cells/metabolism, MESH: Cells, MESH: Middle Aged, Cultured, Membrane Glycoproteins, MESH: HIV Infections/drug therapy, MESH: Macrophages/immunology, Antibodies, Monoclonal, MESH: Viremia/drug therapy, MESH: Macrophages/drug effects, Middle Aged, Flow Cytometry, MESH: Young Adult, MESH: Dendritic Cells/immunology, Antigens, Surface, MESH: Dendritic Cells/drug effects, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Antigens, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Macrophage Activation/drug effects, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Anti-HIV Agents, MESH: Monocytes/immunology, MESH: Tumor Necrosis Factor-alpha/metabolism, MESH: Glycoproteins, MESH: Viremia/immunology, MESH: Lipopolysaccharides/toxicity, Humans, MESH: Macrophages/metabolism, Glycoproteins, MESH: Humans, CD1, MESH: Antibodies, Monoclonal/metabolism, Macrophages, MESH: HIV Infections/metabolism, MESH: Viremia/metabolism, MESH: Adult, MESH: HIV Infections/immunology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Dendritic Cells, Macrophage Activation, MESH: Male, MESH: Macrophages/pathology, MESH: Dendritic Cells/pathology Female, MESH: Viremia/pathology
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