Human immunodeficiency virus type 1 gp120 induces abnormal maturation and functional alterations of dendritic cells: a novel mechanism for AIDS pathogenesis.
Dendritic cells (DCs) play a crucial role in bridging innate and acquired immune responses to pathogens. In human immunodeficiency virus type 1 (HIV-1) infection, immature DCs (iDCs) are also main targets for HIV-1 at the mucosal level. In this study, we evaluated the effects of HIV-1-DC interactions on the maturation and functional activity of these cells. Exposure of human monocyte-derived iDCs to either aldrithiol-2-inactivated HIV-1 or gp120 led to an upmodulation of activation markers indicative of functional maturation. Despite their phenotype, these cells retained antigen uptake capacity and showed an impaired ability to secrete cytokines or chemokines and to induce T-cell proliferation. Although gp120 did not interfere with DC differentiation, the capacity of these cells to produce interleukin-12 (IL-12) upon maturation was markedly reduced. Likewise, iDCs stimulated by classical maturation factors in the presence of gp120 lacked allostimulatory capacity and did not produce IL-12, in spite of their phenotype typical of activated DCs. Exogenous addition of IL-12 restores the allostimulatory capacity of gp120-exposed DCs. The finding that gp120 induces abnormal maturation of DCs linked to profound suppression of their activities unravels a novel mechanism by which HIV can lead to immune dysfunction in AIDS patients.
Fantuzzi
Laura
L
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Purificato
Cristina
C
Donato
Karim
K
Belardelli
Filippo
F
Gessani
Sandra
S
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology* / Q000502:physiology / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis; D007519:Isoantigens; D008954:Models, Biological; D010641:Phenotype; D038301:Virus Inactivation
D015699:HIV Envelope Protein gp120; D007519:Isoantigens; D018664:Interleukin-12