CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBß to drive IL1α and IL1ß expression.
Immunology
; 160(1): 64-77, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32064589
ABSTRACT
Sterile inflammation contributes to many pathological states associated with mitochondrial injury. Mitochondrial injury disrupts calcium homeostasis and results in the release of CpG-rich mitochondrial DNA. The role of CpG-stimulated TLR9 innate immune signalling and sterile inflammation is well studied; however, how calcium dyshomeostasis affects this signalling is unknown. Therefore, we interrogated the relationship beτween intracellular calcium and CpG-induced TLR9 signalling in murine macrophages. We found that CpG-ODN-induced NFκB-dependent IL1α and IL1ß expression was significantly attenuated by both calcium chelation and calcineurin inhibition, a finding mediated by inhibition of degradation of the NFκB inhibitory protein IκBß. In contrast, calcium ionophore exposure increased CpG-induced IκBß degradation and IL1α and IL1ß expression. These results demonstrate that through its effect on IκBß degradation, increased intracellular Ca2+ drives a pro-inflammatory TLR9-mediated innate immune response. These results have implications for the study of innate immune signalling downstream of mitochondrial stress and injury.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Calcio
/
Señalización del Calcio
/
Proteínas I-kappa B
/
Receptor Toll-Like 9
/
Inmunidad Innata
Límite:
Animals
Idioma:
En
Revista:
Immunology
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos