Abstract
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-α 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-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.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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0648-3) contains supplementary material, which is available to authorized users.
Highlights
The innate immune system recognizes pathogens via its pattern recognition receptors
A compelling body of evidence showing that members of the nucleotide-binding oligomerization domain (NOD) family of proteins play a critical role in the immune response following pathogen invasion has accumulated, and at least two members of this family of proteins appear to sense the cytoplasmic microbial pathogen-associated molecular patterns (PAMPs) of the invading microbes and to initiate the activation of the innate immune system, which leads to inflammation [8,9,10]
S. pneumoniae-induced NOD2 mRNA expression in the brain tissue To determine whether the murine brain tissue expressed these novel pattern recognition receptors, we assessed the NOD1 and NOD2 mRNA levels in the uninfected and S. pneumoniae-infected murine brains
Summary
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. A compelling body of evidence showing that members of the nucleotide-binding oligomerization domain (NOD) family of proteins play a critical role in the immune response following pathogen invasion has accumulated, and at least two members of this family of proteins appear to sense the cytoplasmic microbial pathogen-associated molecular patterns (PAMPs) of the invading microbes and to initiate the activation of the innate immune system, which leads to inflammation [8,9,10]. The expressions of these novel bacterial pattern recognition receptors have not been established within the central nervous system (CNS) in vivo
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