Research on the role of S100A6 protein in Streptococcus agalactiae-induced neonatal meningitis
10.3760/cma.j.cn112309-20240709-00254
- VernacularTitle:S100A6蛋白在无乳链球菌致新生儿脑膜炎中的作用探索
- Author:
Chengdong XIAO
1
;
Mujie ZHANG
;
Xiaoyan TIAN
;
Jiaxin LIANG
;
Shiyu SU
;
Yucheng HUANG
;
Liang PENG
Author Information
1. 广州医科大学附属第五医院，广东高校生物靶向诊治与康复重点实验室，广州 510700
- Publication Type:Journal Article
- Keywords:
Streptococcus;
Meningitis;
S100A6;
Central nervous system infection
- From:
Chinese Journal of Microbiology and Immunology
2025;45(8):657-663
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role and molecular mechanisms of S100A6 protein in neonatal meningitis caused by Streptococcus agalactiae. Methods:Human brain microvascular endothelial cells (HBMECs) were used as an in vitro experimental model, and siRNA was employed to construct S100A6 gene knockdown HBMECs strain. The S100A6 gene overexpression cell line was established by lentiviral transfection method. Western blot was used to detect the expression level of S100A6 protein in HBMECs after Streptococcus agalactiae infection, and the change in intracellular inflammatory cytokine protein levels after S100A6 gene knockdown or overexpression. A neonatal bacterial meningitis model was established by injecting Streptococcus agalactiae suspension into the cisterna magna of neonatal Sprague-Dawley (SD) rats. HE staining was used to observe pathological changes in brain tissue; immunohistochemistry was used to detect the expression and distribution of S100A6 protein in brain tissue; Western blot and ELISA were used to measure S100A6 protein levels in cerebrospinal fluid (CSF). Results:Compared with the control group, the intracellular S100A6 protein level in HBMECs increased significantly following Streptococcus cgalactiae infection. After S100A6 gene knockdown, the invasion rate of Streptococcus agalactiae into the HBMECs was significantly reduced ( P<0.01), while intracellular TNF-α and IL-6 protein levels were elevated markedly ( P<0.01). In contrast, overexpression of S100A6 gene increased the invasion rate ( P<0.01) and notably decreased TNF-α and IL-6 protein levels ( P<0.001). In the neonatal SD rat bacterial meningitis model, HE staining revealed substantial neutrophil infiltration in brain tissue after Streptococcus agalactiae infection. Immunohistochemistry showed extensive deposition of S100A6 protein around the meninges, and significant expression of S100A6 protein was also detected in CSF. Conclusions:S100A6 protein is crucial in mediating neonatal meningitis caused by Streptococcus agalactiae infection. S100A6 gene knockdown promotes the production of intracellular inflammatory cytokines and reduces Streptococcus agalactiae invasion into cells, thereby alleviating bacteria-induced cellular damage. Additionally, the increased expression of S100A6 protein in brain tissue and CSF after Streptococcus agalactiae infection suggests its potential as a diagnostic biomarker for bacterial meningitis.
