Pivotal role of M-DC8⁺ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products.
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.
Inserm U1016, Institut Cochin, Paris, France.
Charles-Antoine
CA
Dutertre
Sonia
S
Amraoui
Annalisa
A
DeRosa
Jean-Pierre
JP
Jourdain
Lene
L
Vimeux
Matthieu
M
Goguet
Séverine
S
Degrelle
Vincent
V
Feuillet
Anne-Sophie
AS
Liovat
Michaela
M
Müller-Trutwin
Nipa
N
Decroix
Christiane
C
Deveau
Laurence
L
Meyer
Cécile
C
Goujard
Pierre
P
Loulergue
Odile
O
Launay
Yolande
Y
Richard
Anne
A
Hosmalin
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D018949:Antigens, CD1; D000954:Antigens, Surface / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; D006023:Glycoproteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; C546931:THBD protein, human; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha