PMID- 15331709 OWN - NLM STAT- MEDLINE DCOM- 20040928 LR - 20181113 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 78 IP - 18 DP - 2004 Sep TI - Human immunodeficiency virus type 1 gp120 induces abnormal maturation and functional alterations of dendritic cells: a novel mechanism for AIDS pathogenesis. PG - 9763-72 AB - 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. CI - Copyright 2004 American Society for Microbiology FAU - Fantuzzi, Laura AU - Fantuzzi L AD - Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy. FAU - Purificato, Cristina AU - Purificato C FAU - Donato, Karim AU - Donato K FAU - Belardelli, Filippo AU - Belardelli F FAU - Gessani, Sandra AU - Gessani S LA - eng GR - R21 AI054215/AI/NIAID NIH HHS/United States GR - 1 R21 AI054215-01/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (HIV Envelope Protein gp120) RN - 0 (Isoantigens) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Acquired Immunodeficiency Syndrome/*etiology/immunology MH - Cell Differentiation MH - Dendritic Cells/immunology/*pathology/physiology/*virology MH - HIV Envelope Protein gp120/*physiology MH - HIV-1/*pathogenicity/physiology MH - Humans MH - In Vitro Techniques MH - Interleukin-12/biosynthesis MH - Isoantigens MH - Models, Biological MH - Phenotype MH - Virus Inactivation PMC - PMC515003 EDAT- 2004/08/28 05:00 MHDA- 2004/09/29 05:00 PMCR- 2004/09/01 CRDT- 2004/08/28 05:00 PHST- 2004/08/28 05:00 [pubmed] PHST- 2004/09/29 05:00 [medline] PHST- 2004/08/28 05:00 [entrez] PHST- 2004/09/01 00:00 [pmc-release] AID - 78/18/9763 [pii] AID - 0765-04 [pii] AID - 10.1128/JVI.78.18.9763-9772.2004 [doi] PST - ppublish SO - J Virol. 2004 Sep;78(18):9763-72. doi: 10.1128/JVI.78.18.9763-9772.2004.