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Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver
Klopfleisch, Robert ;  Stegemann-Koniszewski, Sabine ;  Mueller, Andreas J. ;  Gruber, Achim D. ;  Knolle, Percy ;  Guzman, Carlos A. ;  Bruder, Dunja

HaupttitelTargeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver
AutorKlopfleisch, Robert
AutorStegemann-Koniszewski, Sabine
AutorMueller, Andreas J.
AutorGruber, Achim D.
AutorKnolle, Percy
AutorGuzman, Carlos A.
AutorBruder, Dunja
Seitenzahl14 S.
Freie SchlagwörterLymphocyte activation; Viral hepatitis; Viral infection
DDC610 Medizin und Gesundheit
Auch erschienen inScientific Reports. - 7 (2017), Artikel Nr. 43985
ZusammenfassungHepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting. As read-outs we used in vivo hepatotropic adenovirus challenge, histology and automated multidimensional fluorescence microscopy (MELC). We show that targeted in vivo antigen delivery to cross-presenting DCs is highly effective in inducing antiviral CTLs capable of eliminating virus-infected hepatocytes, while control vaccine formulation not involving DC targeting failed to induce immunity against hepatotropic virus. Moreover, we observed distinct patterns of CD8+ T cell interaction with virus-infected and apoptotic hepatocytes in the two DC-targeting groups suggesting that the different vaccine formulations may stimulate distinct types of effector functions. Our findings represent an important step toward the future development of vaccines against hepatotropic viruses and the treatment of patients with hepatic virus infection after liver transplantation to avoid reinfection.
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Fachbereich/EinrichtungFB Veterinärmedizin
Erscheinungsjahr2017
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am05.05.2017 - 09:48:40
Letzte Änderung05.05.2017 - 09:51:16
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000026953
DOI10.1038/srep43985
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