Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING.
FASEB J
; 31(7): 3107-3115, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28396343
ABSTRACT
The cyclic dinucleotides, GMP-AMP (cGAMP) and c-di-AMP [bis-(3',5')-cyclic dimeric AMP], are potent type I IFN inducers via STING-TBK1-IRF3 cascade. They are promising adjuvants that promote antigen-specific humoral and cellular immune responses in different preclinical models; however, an optimal outcome of vaccination depends on a balanced immune activation. Here, we characterize the process of IFN-ß induction by c-di-AMP and cGAMP in an in vitro model on the basis of primary mouse dendritic cells. Results obtained show decreased IFN-ß production upon prolonged cell stimulation. We demonstrate that this effect depends on c-di-AMP/cGAMP-mediated down-regulation of stimulator of IFN gene (STING) protein levels. These results were confirmed by using human peripheral blood mononuclear cell-derived dendritic cells. Studies performed to explore the potential mechanism of STING modulation suggested proteolytic degradation to be a contributing factor to the observed decrease in cellular STING levels. Our work contributes to the elucidation of the molecular mode of action of vaccine constituents, which, in turn, is a prerequisite for the rational design of vaccines with predictable efficacy and safety profiles-Rueckert, C., Rand, U., Roy, U., Kasmapour, B., Strowig, T., Guzmán, C. A. Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
/
AMP Cíclico
/
Proteínas de la Membrana
/
Nucleótidos Cíclicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania