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Pivotal role of M-DC8⁺ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products.
- Source :
-
Blood [Blood] 2012 Sep 13; Vol. 120 (11), pp. 2259-68. Date of Electronic Publication: 2012 Jul 16. - Publication Year :
- 2012
-
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.
- Subjects :
- Adult
Anti-HIV Agents therapeutic use
Antigens, CD1
Antigens, Surface metabolism
Cells, Cultured
Dendritic Cells drug effects
Dendritic Cells immunology
Dendritic Cells metabolism
Dendritic Cells pathology
Female
Flow Cytometry
Glycoproteins
HIV Infections drug therapy
HIV Infections immunology
HIV Infections pathology
Humans
Lipopolysaccharides toxicity
Macrophage Activation drug effects
Macrophages drug effects
Macrophages immunology
Macrophages metabolism
Macrophages pathology
Male
Middle Aged
Monocytes drug effects
Monocytes immunology
Monocytes pathology
Thrombomodulin
Viremia drug therapy
Viremia immunology
Viremia pathology
Young Adult
Antibodies, Monoclonal metabolism
HIV Infections metabolism
Membrane Glycoproteins antagonists & inhibitors
Monocytes metabolism
Tumor Necrosis Factor-alpha metabolism
Up-Regulation drug effects
Viremia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 22802339
- Full Text :
- https://doi.org/10.1182/blood-2012-03-418681