Počet záznamů: 1
Antigen Targeting to CD11b+ Dendritic Cells in Association with TLR4/TRIF Signaling Promotes Strong CD8+ T Cell Responses
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SYSNO ASEP 0439962 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Antigen Targeting to CD11b+ Dendritic Cells in Association with TLR4/TRIF Signaling Promotes Strong CD8+ T Cell Responses Tvůrce(i) Dadaglio, G. (FR)
Fayolle, C. (FR)
Zhang, X. (FR)
Ryffel, B. (FR)
Oberkampf, M. (FR)
Felix, T. (FR)
Hervas-Stubbs, S. (ES)
Osička, Radim (MBU-M) RID, ORCID
Šebo, Peter (MBU-M) RID, ORCID
Ladant, D. (FR)
Leclerc, C. (FR)Celkový počet autorů 11 Zdroj.dok. Journal of Immunology. - : American Association of Immunologists - ISSN 0022-1767
Roč. 193, č. 2 (2014), s. 1787-1798Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova antigen ; dendritic cells ; receptors Vědní obor RIV EE - Mikrobiologie, virologie CEP GAP302/11/0580 GA ČR - Grantová agentura ČR GAP302/12/0460 GA ČR - Grantová agentura ČR Institucionální podpora MBU-M - RVO:61388971 UT WOS 000341139300030 Anotace Deciphering the mechanisms that allow the induction of strong immune responses is crucial to developing efficient vaccines against infectious diseases and cancer. Based on the discovery that the adenylate cyclase from Bordetella pertussis binds to the CD11b/CD18 integrin, we developed a highly efficient detoxified adenylate cyclase-based vector (CyaA) capable of delivering a large variety of Ags to the APC. This vector allows the induction of protective and therapeutic immunity against viral and tumoral challenges as well as against transplanted tumors in the absence of any added adjuvant. Two therapeutic vaccine candidates against human papilloma viruses and melanoma have been developed recently, based on the CyaA vector, and are currently in clinical trials. We took advantage of one of these highly purified vaccines, produced under good manufacturing practice-like conditions, to decipher the mechanisms by which CyaA induces immune responses. In this study, we demonstrate that CyaA binds both human and mouse CD11b(+) dendritic cells (DCs) and induces their maturation, as shown by the upregulation of costimulatory and MHC molecules and the production of proinflammatory cytokines. Importantly, we show that DCs sense CyaA through the TLR4/Toll/IL-1R domain-containing adapter-inducing IFN-beta pathway, independent of the presence of LPS. These findings show that CyaA possesses the intrinsic ability to not only target DCs but also to activate them, leading to the induction of strong immune responses. Overall, this study demonstrates that Ag delivery to CD11b(+) DCs in association with TLR4/Toll/IL-1R domain-containing adapter-inducing IFN-b activation is an efficient strategy to promote strong specific CD8(+) T cell responses. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2015
Počet záznamů: 1