NOD2 regulates microglial inflammation through the TAK1-NF-κB pathway and autophagy activation in murine pneumococcal meningitis.
Brain Res Bull
; 158: 20-30, 2020 05.
Article
in En
| MEDLINE
| ID: mdl-32109527
ABSTRACT
Streptococcus pneumoniae is responsible for pneumococcal meningitis, with significant mortality and morbidity worldwide. Microglial inï¬ammation plays a vital role in meningitis. The peptidoglycan sensor NOD2 (nucleotide-binding oligomerization domain 2) has been identiï¬ed to promote microglia activation, but the role in autophagy following pneumococcal meningitis remains unclear. In the present study, we investigated the role of NOD2 in microglial inï¬ammation and autophagy, as well as related signaling pathways, during S. pneumonia infection. NOD2 expression was knocked down by the injection of lentivirus-mediated short-hairpin RNA (shRNA). Our results revealed that NOD2 promotes microglial inï¬ammation by increasing inflammatory mediators. We also showed that the TAK1-NF-κB pathway is involved in this process. In addition, NOD2 increased the expression of autophagy-related proteins and induced autophagosome formation. Rapamycin and 3-MA were utilized to assess the role of autophagy in microglial inflammation induced by S. pneumonia. We demonstrated that autophagy serves as a cellular defense mechanism to reduce inflammatory mediators. Similar to the in vitro results, NOD2 induced inï¬ammation and autophagy in the brain in a mouse meningitis model. Moreover, NOD2 silencing signiï¬cantly reduced brain edema and improved the neurological function of pneumococcal meningitis mice. Taken together, these data demonstrate that NOD2 promotes microglial inï¬ammation and autophagy in murine pneumococcal meningitis, and the TAK1-NF-κB pathway is involved in microglial activation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
NF-kappa B
/
Microglia
/
MAP Kinase Kinase Kinases
/
Nod2 Signaling Adaptor Protein
/
Meningitis, Pneumococcal
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Brain Res Bull
Year:
2020
Document type:
Article