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Updated: Apr 20, 2026

Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Analysis of nucleotide-binding oligomerization domain proteins in a murine model of pneumococcal meningitis
Xinjie Liu1,2, Qizheng Han3, Junhong Leng4
1Department of Pediatrics, Qilu Hospital, Shandong University, No. 107 Wen Hua Xi Road, Jinan, People's Republic of China. liuxinjie@sdu.edu.cn.
Background:
The innate immune system recognizes pathogens via its pattern recognition receptors. The objective of this study was to investigate the role of the nucleotide-binding oligomerization domain (NOD) proteins, a family of the novel bacterial pattern recognition receptors, in host responses to the gram-positive bacteria Streptococcus pneumoniae.
Methods:
Sprague-Dawley rats were infected via intracisternal injections of viable S. pneumoniae, and rats in the control group were injected with sterile saline. After infection, real-time PCR was performed to determine the presence of mRNAs encoding NOD1 and NOD2. Quantitative analyses of the NOD1, NOD2 and NF-kB proteins were also performed western blotting following challenge infections with viable S. pneumoniae. The TNF-α and IL-6 levels in brain homogenates were evaluated using enzyme-linked immunosorbent assays (ELISAs).
Results:
The results revealed up-regulations of the mRNA and protein levels of NOD2 within the CNS of rats with S. pneumoniae meningitis. Moreover, the activation of NF-κB in the brain tissues following infection with live S. pneumoniae was also significantly increased, which indicates that NOD2 mediated NF-κB activation in experimental pneumococcal meningitis. Similarly, TNF-α and IL-6 levels were increased in the brain following in vivo S. pneumoniae administration.
Conclusions:
These results suggest that NOD2 is involved in the host response to the gram-positive bacteria S. pneumoniae in the CNS and that NOD2 might play an important role in the initiation and/or progression of CNS inflammation associated with pneumococcal meningitis.
Insights
Nucleotide-binding oligomerization domain (NOD) 2 is upregulated in the central nervous system during Streptococcus pneumoniae infection. This suggests NOD2 plays a role in host responses and inflammation in pneumococcal meningitis.
Area of Science:
- Immunology
- Microbiology
- Neuroscience
Background:
- The innate immune system uses pattern recognition receptors (PRRs) to detect pathogens.
- Nucleotide-binding oligomerization domain (NOD) proteins are a novel class of bacterial PRRs.
Purpose of the Study:
- To investigate the role of NOD proteins in host responses to Streptococcus pneumoniae.
- To understand NOD protein involvement in central nervous system (CNS) inflammation.
Main Methods:
- Rat model of Streptococcus pneumoniae meningitis induced by intracisternal injection.
- Real-time PCR to quantify NOD1 and NOD2 mRNA expression.
- Western blotting for NOD1, NOD2, and NF-κB protein levels.
- ELISA to measure TNF-α and IL-6 levels in brain homogenates.
Main Results:
- NOD2 mRNA and protein levels were significantly upregulated in the CNS of infected rats.
- NF-κB activation in brain tissue increased, indicating NOD2-mediated signaling.
- Pro-inflammatory cytokines TNF-α and IL-6 levels were elevated in the brain.
Conclusions:
- NOD2 is involved in the host immune response to Streptococcus pneumoniae in the CNS.
- NOD2 may contribute to the initiation and progression of inflammation in pneumococcal meningitis.
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