Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway.
dc.contributor.author | Lirussi, Darío | |
dc.contributor.author | Ebensen, Thomas | |
dc.contributor.author | Schulze, Kai | |
dc.contributor.author | Trittel, Stephanie | |
dc.contributor.author | Duran, Veronica | |
dc.contributor.author | Liebich, Ines | |
dc.contributor.author | Kalinke, Ulrich | |
dc.contributor.author | Guzmán, Carlos Alberto | |
dc.date.accessioned | 2017-08-03T13:05:38Z | |
dc.date.available | 2017-08-03T13:05:38Z | |
dc.date.issued | 2017-07-19 | |
dc.identifier.citation | Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway. 2017 EBioMedicine | en |
dc.identifier.issn | 2352-3964 | |
dc.identifier.pmid | 28754303 | |
dc.identifier.doi | 10.1016/j.ebiom.2017.07.016 | |
dc.identifier.uri | http://hdl.handle.net/10033/621037 | |
dc.description.abstract | Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8(+) cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation. | |
dc.language.iso | en | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.title | Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany. | en |
dc.identifier.journal | EBioMedicine | en |
refterms.dateFOA | 2018-06-12T17:22:18Z | |
html.description.abstract | Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8(+) cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation. |