Cadmium induced immunosuppression through TLR-IκBα-NFκB signaling by promoting autophagic degradation.
Ecotoxicol Environ Saf
; 259: 115017, 2023 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-37196523
ABSTRACT
Environmental and occupational exposure to cadmium (Cd) poses a serious threat to human health. Recent studies indicate that Cd perturbs the immune system and increases the risk of pathogenicity and mortality of bacterial or virus infection. However, the underlying mechanism of Cd-modulated immune responses remains unclear. In this study, we aim to investigate the role of Cd in the immune function of mouse spleen tissues and its primary T cells with Concanavalin A (ConA, a well-known T cell mitogen) activation condition, and elucidate the molecular mechanism. The results showed that Cd exposure inhibited ConA-induced the expressions of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in mouse spleen tissues. Furthermore, the transcriptomic profile by RNA-sequence reveals that (1) Cd exposure can alter immune system process; (2) Cd may affect the NFκB signaling pathway. Both in vitro and in vivo results showed that Cd exposure reduced ConA-activated toll-like receptor 9 (TLR9)-IκBα-NFκB signaling, and the expressions of TLR9, TNF-α and IFN-γ, which were effectively reversed by autophagy-lysosomal inhibitors. All these results confirmedly demonstrated that, by promoting the autophagy-lysosomal degradation of TLR9, Cd suppressed immune response under ConA activation condition. This study provides insight on the mechanism of Cd immunnotoxicity, which might contribute to the prevention of Cd toxicity in the future.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cadmio
/
Receptor Toll-Like 9
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Año:
2023
Tipo del documento:
Article
País de afiliación:
China