NOD2-RIP2 contributes to the inflammatory responses of mice in vivo to Streptococcus pneumoniae.

The objectives of this study were to investigate the role of the NOD2-RIP2 pathway in host responses to the gram-positive bacteria Streptococcus pneumoniae and to evaluate the effect of the RIP2 inhibitor gefitinib in a mouse model of S. pneumoniae meningitis. Mice were randomly divided into a normal saline control group (NS group), an S. pneumoniae meningitis group (SP group), a gefitinib group and a vehicle group. Animals in the NS group were sham-infected with sterile saline. Mice in the other three groups were inoculated with S. pneumoniae and left untreated, treated with gefitinib, or treated with vehicle. The results revealed upregulation of the mRNA and protein levels of NOD2, RIP2, NF-κB, TNF-α and IL-6 within the CNS of mice with S. pneumoniae meningitis. Moreover, mice in the meningitis group were severely ill and demonstrated a significant loss of neurons. Treatment with the RIP2 inhibitor gefitinib showed less intense activation of NF-kB, decreased TNF-α and IL-6, attenuated neuronal injury and improved illness. These results suggest that NOD2-RIP2 is involved in the host response to the gram-positive bacteria S. pneumoniae in the CNS and that the RIP2 inhibitor gefitinib protects the brain from damage caused by S. pneumoniae.