Pivotal role of M-DC8⁺ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products

Blood. 2012 Sep 13;120(11):2259-68. doi: 10.1182/blood-2012-03-418681. Epub 2012 Jul 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Monoclonal / metabolism*
  • 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 / metabolism*
  • HIV Infections / pathology
  • Humans
  • Lipopolysaccharides / toxicity
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation* / drug effects
  • Viremia / drug therapy
  • Viremia / immunology
  • Viremia / metabolism*
  • Viremia / pathology
  • Young Adult

Substances

  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Antigens, CD1
  • Antigens, Surface
  • CD1C protein, human
  • Glycoproteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Tumor Necrosis Factor-alpha
  • blood dendritic cell antigen 3, human