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

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 suggeste...

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Autores principales: Lirussi, Darío, Ebensen, Thomas, Schulze, Kai, Trittel, Stephanie, Duran, Veronica, Liebich, Ines, Kalinke, Ulrich, Guzmán, Carlos A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552247/
https://www.ncbi.nlm.nih.gov/pubmed/28754303
http://dx.doi.org/10.1016/j.ebiom.2017.07.016
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author Lirussi, Darío
Ebensen, Thomas
Schulze, Kai
Trittel, Stephanie
Duran, Veronica
Liebich, Ines
Kalinke, Ulrich
Guzmán, Carlos A.
author_facet Lirussi, Darío
Ebensen, Thomas
Schulze, Kai
Trittel, Stephanie
Duran, Veronica
Liebich, Ines
Kalinke, Ulrich
Guzmán, Carlos A.
author_sort Lirussi, Darío
collection PubMed
description 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.
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spelling pubmed-55522472017-08-22 Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway Lirussi, Darío Ebensen, Thomas Schulze, Kai Trittel, Stephanie Duran, Veronica Liebich, Ines Kalinke, Ulrich Guzmán, Carlos A. EBioMedicine Research Paper 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. Elsevier 2017-07-19 /pmc/articles/PMC5552247/ /pubmed/28754303 http://dx.doi.org/10.1016/j.ebiom.2017.07.016 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Lirussi, Darío
Ebensen, Thomas
Schulze, Kai
Trittel, Stephanie
Duran, Veronica
Liebich, Ines
Kalinke, Ulrich
Guzmán, Carlos A.
Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway
title Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway
title_full Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway
title_fullStr Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway
title_full_unstemmed Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway
title_short Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway
title_sort type i ifn and not tnf, is essential for cyclic di-nucleotide-elicited ctl by a cytosolic cross-presentation pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552247/
https://www.ncbi.nlm.nih.gov/pubmed/28754303
http://dx.doi.org/10.1016/j.ebiom.2017.07.016
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