Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621037
Title:
Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway.
Authors:
Lirussi, Darío; Ebensen, Thomas; Schulze, Kai ( 0000-0003-2286-3416 ) ; Trittel, Stephanie; Duran, Veronica; Liebich, Ines; Kalinke, Ulrich; Guzmán, Carlos Alberto
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway. 2017 EBioMedicine
Journal:
EBioMedicine
Issue Date:
19-Jul-2017
URI:
http://hdl.handle.net/10033/621037
DOI:
10.1016/j.ebiom.2017.07.016
PubMed ID:
28754303
Type:
Article
Language:
en
ISSN:
2352-3964
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC); publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorLirussi, Daríoen
dc.contributor.authorEbensen, Thomasen
dc.contributor.authorSchulze, Kaien
dc.contributor.authorTrittel, Stephanieen
dc.contributor.authorDuran, Veronicaen
dc.contributor.authorLiebich, Inesen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorGuzmán, Carlos Albertoen
dc.date.accessioned2017-08-03T13:05:38Z-
dc.date.available2017-08-03T13:05:38Z-
dc.date.issued2017-07-19-
dc.identifier.citationType I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway. 2017 EBioMedicineen
dc.identifier.issn2352-3964-
dc.identifier.pmid28754303-
dc.identifier.doi10.1016/j.ebiom.2017.07.016-
dc.identifier.urihttp://hdl.handle.net/10033/621037-
dc.description.abstractCyclic 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleType I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalEBioMedicineen
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