Neonatal Meningitis-Causing Escherichia coli Induces Microglia Activation which Acts as a Double-Edged Sword in Bacterial Meningitis.
Yingying SuGuozhen MaYangyang ZhengJingliang QinXiaoya LiQianwen GeHao SunBin LiuPublished in: International journal of molecular sciences (2023)
Bacterial meningitis is a devastating disease occurring worldwide, with up to half of survivors left with permanent neurological sequelae. Neonatal meningitis-causing Escherichia coli (NMEC) is the most common Gram-negative bacillary organism that causes meningitis, particularly during the neonatal period. Here, RNA-seq transcriptional profiles of microglia in response to NMEC infection show that microglia are activated to produce inflammatory factors. In addition, we found that the secretion of inflammatory factors is a double-edged sword that promotes polymorphonuclear neutrophil (PMN) recruitment to the brain to clear the pathogens but, at the same time, induces neuronal damage, which may be related to the neurological sequelae. New neuroprotective therapeutic strategies must be developed for the treatment of acute bacterial meningitis. We found that transforming growth factor-β (TGF-β) may be a strong candidate in the treatment of acute bacterial meningitis, as it shows a therapeutic effect on bacterial-meningitis-induced brain damage. Prevention of disease and early initiation of the appropriate treatment in patients with suspected or proven bacterial meningitis are the key factors in reducing morbidity and mortality. Novel antibiotic and adjuvant treatment strategies must be developed, and the main goal for new therapies will be dampening the inflammatory response. Based on this view, our findings may help develop novel strategies for bacterial meningitis treatment.
Keyphrases
- cerebrospinal fluid
- inflammatory response
- escherichia coli
- transforming growth factor
- gram negative
- rna seq
- cerebral ischemia
- single cell
- gene expression
- epithelial mesenchymal transition
- multidrug resistant
- liver failure
- transcription factor
- respiratory failure
- combination therapy
- drug induced
- early stage
- neuropathic pain
- multiple sclerosis
- intensive care unit
- white matter
- lipopolysaccharide induced
- staphylococcus aureus
- lps induced
- biofilm formation
- brain injury
- signaling pathway
- high glucose
- candida albicans
- mechanical ventilation
- acute respiratory distress syndrome