title: Natural killer cells support the induction of protective immunity during dendritic cell-mediated vaccination against Leishmania major.
abstract: Dendritic cell (DC)-mediated vaccination against Leishmania major induces a parasite-specific T helper 1 (Th1) response and long-lasting protective immunity in susceptible mice. As the cytokine interleukin-12 required for induction of this Th1 response is not derived from the transferred DC, but has to be produced by the vaccinated host, we examined cross-presentation of transferred DC via resident DC of the host and cross-activation with natural killer (NK) cells as mechanisms supporting the induction of protective immunity after DC-mediated vaccination. Co-culture with DC that had been conditioned ex vivo by loading with L. major lysate and stimulation with CpG-containing oligodeoxynucleotides did not result in the activation of naive DC in vitro. Furthermore, L. major antigen from conditioned DC was not cross-presented to a significant extent in vivo. In contrast, co-culture of DC with NK cells led to cross-activation of both cell populations with induction of interferon-γ, which was dependent on the activation status of the conditioned DC. Transient depletion of NK cells during vaccination of L. major-susceptible mice with conditioned DC resulted in reduced protection. Our findings indicate that cross-presentation of conditioned DC after DC-based vaccination against L. major plays a minor role in the induction of protective immunity. However, we demonstrated for the first time that the capacity of DC to mediate protection against L. major is supported by cross-activation with NK cells of the host and NK-cell-derived interferon-γ.
authors.affiliation: University of Würzburg, Institute for Molecular Infection Biology, Würzburg, Germany.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Remer
authors.forename: Bianca
authors.initials: B
authors.lastname: Roeger
authors.forename: Christine
authors.initials: C
authors.lastname: Hambrecht
authors.forename: Heidrun
authors.initials: H
authors.lastname: Moll
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D007371:Interferon-gamma