This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fantuzzi, L.
Right arrow Articles by Gessani, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fantuzzi, L.
Right arrow Articles by Gessani, S.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 9763-9772, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9763-9772.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 gp120 Induces Abnormal Maturation and Functional Alterations of Dendritic Cells: a Novel Mechanism for AIDS Pathogenesis

Laura Fantuzzi, Cristina Purificato, Karim Donato, Filippo Belardelli, and Sandra Gessani*

Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy

Received 1 April 2004/ Accepted 17 May 2004

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.

* Corresponding author. Mailing address: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39-06-49903169. Fax: 39-06-49902097. E-mail: gessani{at}iss.it.

Journal of Virology, September 2004, p. 9763-9772, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9763-9772.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fantuzzi, L., Spadaro, F., Purificato, C., Cecchetti, S., Podo, F., Belardelli, F., Gessani, S., Ramoni, C. (2008). Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB-driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages. Blood 111: 3355-3363 [Abstract] [Full Text]  
  • Balkow, S., Krux, F., Loser, K., Becker, J. U., Grabbe, S., Dittmer, U. (2007). Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naive T cells, and favors expansion of regulatory T cells. Blood 110: 3949-3958 [Abstract] [Full Text]  
  • Lichterfeld, M., Kavanagh, D. G., Williams, K. L., Moza, B., Mui, S. K., Miura, T., Sivamurthy, R., Allgaier, R., Pereyra, F., Trocha, A., Feeney, M., Gandhi, R. T., Rosenberg, E. S., Altfeld, M., Allen, T. M., Allen, R., Walker, B. D., Sundberg, E. J., Yu, X. G. (2007). A viral CTL escape mutation leading to immunoglobulin-like transcript 4 mediated functional inhibition of myelomonocytic cells. JEM 204: 2813-2824 [Abstract] [Full Text]  
  • Freer, G., Matteucci, D., Mazzetti, P., Tarabella, F., Catalucci, V., Bendinelli, M. (2007). Effects of feline immunodeficiency virus on feline monocyte-derived dendritic cells infected by spinoculation. J. Gen. Virol. 88: 2574-2582 [Abstract] [Full Text]  
  • Majumder, B., Venkatachari, N. J., Schafer, E. A., Janket, M. L., Ayyavoo, V. (2007). Dendritic Cells Infected with vpr-Positive Human Immunodeficiency Virus Type 1 Induce CD8+ T-Cell Apoptosis via Upregulation of Tumor Necrosis Factor Alpha. J. Virol. 81: 7388-7399 [Abstract] [Full Text]  
  • Kummer, M., Turza, N. M., Muhl-Zurbes, P., Lechmann, M., Boutell, C., Coffin, R. S., Everett, R. D., Steinkasserer, A., Prechtel, A. T. (2007). Herpes Simplex Virus Type 1 Induces CD83 Degradation in Mature Dendritic Cells with Immediate-Early Kinetics via the Cellular Proteasome. J. Virol. 81: 6326-6338 [Abstract] [Full Text]  
  • Fernando, K., Hu, H., Ni, H., Hoxie, J. A., Weissman, D. (2007). Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses. Blood 109: 2538-2544 [Abstract] [Full Text]  
  • Martinelli, E., Cicala, C., Van Ryk, D., Goode, D. J., Macleod, K., Arthos, J., Fauci, A. S. (2007). HIV-1 gp120 inhibits TLR9-mediated activation and IFN-{alpha} secretion in plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA 104: 3396-3401 [Abstract] [Full Text]  
  • Harman, A. N., Wilkinson, J., Bye, C. R., Bosnjak, L., Stern, J. L., Nicholle, M., Lai, J., Cunningham, A. L. (2006). HIV Induces Maturation of Monocyte-Derived Dendritic Cells and Langerhans Cells. J. Immunol. 177: 7103-7113 [Abstract] [Full Text]  
  • Quaranta, M. G., Mattioli, B., Giordani, L., Viora, M. (2006). The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS. FASEB J. 20: 2198-2208 [Abstract] [Full Text]  
  • Chougnet, C., Gessani, S. (2006). Role of gp120 in dendritic cell dysfunction in HIV infection. J. Leukoc. Biol. 80: 994-1000 [Abstract] [Full Text]  
  • Mavilio, D., Lombardo, G., Kinter, A., Fogli, M., La Sala, A., Ortolano, S., Farschi, A., Follmann, D., Gregg, R., Kovacs, C., Marcenaro, E., Pende, D., Moretta, A., Fauci, A. S. (2006). Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection. JEM 203: 2339-2350 [Abstract] [Full Text]  
  • Tomkowicz, B., Lee, C., Ravyn, V., Cheung, R., Ptasznik, A., Collman, R. G. (2006). The Src kinase Lyn is required for CCR5 signaling in response to MIP-1beta and R5 HIV-1 gp120 in human macrophages. Blood 108: 1145-1150 [Abstract] [Full Text]  
  • Schneider-Schaulies, S., Dittmer, U. (2006). Silencing T cells or T-cell silencing: concepts in virus-induced immunosuppression. J. Gen. Virol. 87: 1423-1438 [Abstract] [Full Text]  
  • Holl, V., Peressin, M., Schmidt, S., Decoville, T., Zolla-Pazner, S., Aubertin, A.-M., Moog, C. (2006). Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti-HIV-1 IgG without induction of maturation. Blood 107: 4466-4474 [Abstract] [Full Text]  
  • Ancuta, P., Autissier, P., Wurcel, A., Zaman, T., Stone, D., Gabuzda, D. (2006). CD16+ Monocyte-Derived Macrophages Activate Resting T Cells for HIV Infection by Producing CCR3 and CCR4 Ligands. J. Immunol. 176: 5760-5771 [Abstract] [Full Text]  
  • Zhang, R., Lifson, J. D., Chougnet, C. (2006). Failure of HIV-exposed CD4+ T cells to activate dendritic cells is reversed by restoration of CD40/CD154 interactions. Blood 107: 1989-1995 [Abstract] [Full Text]  
  • Del Corno, M., Gauzzi, M. C., Penna, G., Belardelli, F., Adorini, L., Gessani, S. (2005). Human Immunodeficiency Virus Type 1 gp120 and Other Activation Stimuli Are Highly Effective in Triggering Alpha Interferon and CC Chemokine Production in Circulating Plasmacytoid but Not Myeloid Dendritic Cells. J. Virol. 79: 12597-12601 [Abstract] [Full Text]  
  • Peretti, S., Shaw, A., Blanchard, J., Bohm, R., Morrow, G., Lifson, J. D., Gettie, A., Pope, M. (2005). Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses. Blood 106: 1305-1313 [Abstract] [Full Text]  
  • Majumder, B., Janket, M. L., Schafer, E. A., Schaubert, K., Huang, X.-L., Kan-Mitchell, J., Rinaldo, C. R. Jr., Ayyavoo, V. (2005). Human Immunodeficiency Virus Type 1 Vpr Impairs Dendritic Cell Maturation and T-Cell Activation: Implications for Viral Immune Escape. J. Virol. 79: 7990-8003 [Abstract] [Full Text]  
  • Gurney, K. B., Elliott, J., Nassanian, H., Song, C., Soilleux, E., McGowan, I., Anton, P. A., Lee, B. (2005). Binding and Transfer of Human Immunodeficiency Virus by DC-SIGN+ Cells in Human Rectal Mucosa. J. Virol. 79: 5762-5773 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»