HIV-1 capture and antigen presentation by dendritic cells: Enhanced viral capture does not correlate with better T cell activation

Maria T. Rodriguez-Plata, Alejandra Urrutia, Sylvain Cardinaud, Maria J. Buzón, Nuria Izquierdo-Useros, Julia G. Prado, Maria C. Puertas, Itziar Erkizia, Pierre Grégoire Coulon, Samandhy Cedeño, Bonaventura Clotet, Arnaud Moris, Javier Martinez-Picado

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18 Citations (Scopus)

Abstract

During HIV-1 infection, dendritic cells (DC) facilitate dissemination of HIV-1 while trying to trigger adaptive antiviral immune responses.We examined whether increased HIV-1 capture in DC matured with LPS results in more efficient Ag presentation to HIV- 1-specific CD4 + and CD8 + T cells. To block the DC-mediated trans-infection of HIV-1 and maximize Ag loading, we also evaluated a noninfectious integrase-deficient HIV-1 isolate, HIV NL4-3ΔIN. We showed that higher viral capture of DC did not guarantee better Ag presentation or T cell activation. Greater HIV NL4-3 uptake by fully LPS-matured DC resulted in higher viral transmission to target cells but poorer stimulation of HIV-1-specific CD4 + and CD8 + T cells. Conversely, maturation of DC with LPS during, but not before, viral loading enhanced both HLA-I and HLA-II HIV-1-derived Ag presentation. In contrast, DC maturation with the clinical-grade mixture consisting of IL-1β, TNF-α, IL-6, and PGE 2 during viral uptake only stimulated HIV-1-specific CD8 + T cells. Hence, DC maturation state, activation stimulus, and time lag between DC maturation and Ag loading impact HIV-1 capture and virus Ag presentation. Our results demonstrate a dissociation between the capacity to capture HIV-1 and to present viral Ags. Integrase-deficient HIV NL4-3ΔIN was also efficiently captured and presented by DC through the HLA-I and HLA-II pathways but in the absence of viral dissemination. HIV NL4-3ΔIN seems to be an attractive candidate to be explored. These results provide new insights into DC biology and have implications in the optimization of DC-based immunotherapy against HIV-1 infection. Copyright © 2012 by The American Association of Immunologists, Inc.
Original languageEnglish
Pages (from-to)6036-6045
JournalJournal of Immunology
Volume188
Issue number12
DOIs
Publication statusPublished - 15 Jun 2012

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    Rodriguez-Plata, M. T., Urrutia, A., Cardinaud, S., Buzón, M. J., Izquierdo-Useros, N., Prado, J. G., Puertas, M. C., Erkizia, I., Coulon, P. G., Cedeño, S., Clotet, B., Moris, A., & Martinez-Picado, J. (2012). HIV-1 capture and antigen presentation by dendritic cells: Enhanced viral capture does not correlate with better T cell activation. Journal of Immunology, 188(12), 6036-6045. https://doi.org/10.4049/jimmunol.1200267