title: HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T cell activation.
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.
authors.affiliation: Institut de Recerca de la SIDA IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rodriguez-Plata
authors.forename: Alejandra
authors.initials: A
authors.lastname: Urrutia
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cardinaud
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Buzón
authors.forename: Nuria
authors.initials: N
authors.lastname: Izquierdo-Useros
authors.forename: Julia G
authors.initials: JG
authors.lastname: Prado
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Itziar
authors.initials: I
authors.lastname: Erkizia
authors.forename: Pierre-Grégoire
authors.initials: PG
authors.lastname: Coulon
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeño
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Arnaud
authors.initials: A
authors.lastname: Moris
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D013601:T-Lymphocytes / Q000276:immunology*