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

被引:78
|
作者
Dutertre, Charles-Antoine [1 ,2 ,3 ]
Amraoui, Sonia [1 ,2 ,3 ]
DeRosa, Annalisa [1 ,2 ,3 ]
Jourdain, Jean-Pierre [1 ,2 ,3 ]
Vimeux, Lene [1 ,2 ,3 ]
Goguet, Matthieu [1 ,2 ,3 ]
Degrelle, Severine [1 ,2 ,3 ]
Feuillet, Vincent [1 ,2 ,3 ]
Liovat, Anne-Sophie [4 ]
Mueller-Trutwin, Michaela [4 ]
Decroix, Nipa [5 ,6 ]
Deveau, Christiane [7 ]
Meyer, Laurence [7 ]
Goujard, Cecile [7 ]
Loulergue, Pierre [5 ,6 ]
Launay, Odile [5 ,6 ,8 ]
Richard, Yolande [1 ,2 ,3 ]
Hosmalin, Anne [1 ,2 ,3 ,6 ]
机构
[1] Inserm U1016, Immunohematol Dept, Inst Cochin, F-75014 Paris, France
[2] CNRS, Unite Mixte Rech, F-8104 Paris, France
[3] Univ Paris 05, Paris, France
[4] Inst Pasteur, Unite Regulat Infect Retrovirales, Paris, France
[5] Inserm CIC BT505, Ctr Invest Clin CIC Vaccinol Cochin Pasteur, Paris, France
[6] Hop Cochin, AP HP, Paris, France
[7] Univ Paris Sud, Hop Bicetre, AP HP, Inserm U1018, Le Kremlin Bicetre, France
[8] Univ Paris 05, Fac Med, Paris, France
关键词
COLONY-STIMULATING FACTOR; HUMAN DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE ACTIVATION; 6-SULFO LACNAC; GENE-EXPRESSION; GM-CSF; VIRUS; DEPLETION;
D O I
10.1182/blood-2012-03-418681
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 TNF alpha. 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 TNF alpha 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 TNF alpha 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. (Blood. 2012;120(11):2259-2268)
引用
收藏
页码:2259 / 2268
页数:10
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