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

EBioMedicine

Thomas Ebensen¹  Darío Lirussi¹  Carlos A. Guzmán¹  Kai Schulze¹  Stephanie Trittel¹  Veronica Duran²  Ulrich Kalinke²  Ines Liebich³ 

[1] Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany;Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany;geneXplain GmbH, Wolfenbüttel, Germany;

关键词: Vaccine;    CDN;    CDA;    CTL;    Type I IFN;    Cross-presentation;    Cytosolic pathway;   

DOI  :  10.1016/j.ebiom.2017.07.016

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown