Journal
EBIOMEDICINE
Volume 22, Issue -, Pages 100-111Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2017.07.016
Keywords
Vaccine; CDN; CDA; CTL; Type I IFN; Cross-presentation; Cytosolic pathway
Funding
- EU (UniVax) [601738]
- BMBF [0315890]
- Helmholtz Association (HAI-IDR)
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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-gamma-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 ofMHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-a) 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. (C) 2017 The Authors. Published by Elsevier B.V.
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