Analysis of nucleotide-binding oligomerization domain proteins in a murine model of pneumococcal meningitis

Xinjie Liu, Qizheng Han, Junhong Leng

BackgroundThe 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. MethodsSprague¿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-¿ and IL-6 levels in brain homogenates were evaluated using enzyme-linked immunosorbent assays (ELISAs).ResultsThe 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-¿B in the brain tissues following infection with live S. pneumoniae was also significantly increased, which indicates that NOD2 mediated NF-¿B activation in experimental pneumococcal meningitis. Similarly, TNF-¿ and IL-6 levels were increased in the brain following in vivo S. pneumoniae administration.ConclusionsThese 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.