Plasmacytoid dendritic cells (pDCs) from HIV controllers produce interferon-α and differentiate into functional killer pDCs under HIV activation.
BACKGROUND
Human immunodeficiency virus (HIV) controllers spontaneously control viremia and CD4 T-cell depletion in contrast to viremic patients. After HIV exposure, plasmacytoid dendritic cells (pDCs) produce high levels of interferon alpha (IFN-α) and express the apoptotic ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand). Simian models have shown that prolonged high levels of IFN-α production could be responsible for AIDS progression.


METHODS
We studied pDC activation in response to human immunodeficiency virus (HIV) using flow cytometry and 3D microscopy.


RESULTS
We show here that pDCs from controller patients produced higher levels of IFN-α in response to HIV than pDCs from viremic patients but similar levels to pDCs from healthy donors. Because binding of HIV to CD4 is essential for pDC activation, the low CD4 expression by pDCs from viremic patients may explain the weak IFN-α response to HIV. Three-dimensional microscopy revealed that pDCs from controllers and healthy donors expressed intracellular TRAIL that is relocalized to the membrane after HIV exposure. In contrast, pDCs from viremic patients expressed membrane TRAIL without any stimulation.


CONCLUSIONS
We demonstrate that, in response to HIV, pDCs from controller patients produce IFN-α, express membrane TRAIL, and induce apoptosis of T-cell lines.
Centre National de Recherche Scientifique UMR 8147, Université Paris Descartes, Paris, France.
Lucie
L
Barblu
Kawthar
K
Machmach
Christophe
C
Gras
Jean-François
JF
Delfraissy
Faroudy
F
Boufassa
Manuel
M
Leal
Ezequiel
E
Ruiz-Mateos
Olivier
O
Lambotte
Jean-Philippe
JP
Herbeuval
D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D015331:Cohort Studies; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D005602:France; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D013030:Spain; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000821:virology; D014775:Virus Activation
D016898:Interferon-alpha; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human