Abstract
Streptococcus pneumoniae meningitis is one of the most common disorders seen in clinical practice. It is believed that the brain tissue immune injury is caused by the expression of pattern-recognition receptors (PRR) which can further induce the release of other cytokines and inflammatory cascades. The aim of this study is to investigate the expression of nucleotide-binding oligomerization domain 2 (NOD2) and inflammatory factors in rat brain tissues infected with Streptococcus pneumoniae and its influence on the blood-brain barrier (BBB) permeability. Rats were given an intracranial injection of Streptococcus pneumoniae to construct the Streptococcus pneumoniae meningitis rat models. The expression change curves of NOD2 and inflammatory factors at different time points (0 h, 12 h, 24 h, 48 h, and 7 d) after Streptococcus pneumoniae were evaluated by enzyme-linked immunosorbent assay (ELISA). Western blotting analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were engaged to examine the expression of NOD2. Furthermore, the changing processes of pathological characteristics, nervous system score, cerebral oedema, and BBB permeability were observed. Our results showed that NOD2 expression began to increase in the 12 h after Streptococcus pneumoniae infection group, while the remaining inflammatory factors were not obviously increased. Meanwhile, the levels of NOD2, as well as inflammatory factors IL-1β, TNF-α, and IL-6 were markedly elevated in 24 h and 48 h infection groups, which were consistent with the increases in BBB permeability and BWC, and the positive expression of NOD2 in the infected rat brain tissues was observed using immunohistochemistry (IHC). This study suggests that NOD2 might be related to the activation of inflammation pathways and the damage to the blood-brain barrier. NOD2 and inflammatory factors have played vital roles in the pathogenesis of Streptococcus pneumoniae meningitis.
Highlights
Streptococcus pneumoniae is the common central nervous system infectious pathogen in clinical practice [1, 2]. e overall mortality and prognosis for survivors remain unsatisfactory regardless of the application of effective antibiotics and the promotion of effective vaccination [3, 4]
20 members of the NOD family have been reported, such as apoptotic protease-activating factor-1 (APAF-1), nucleotide-binding oligomerization domain 1 (NOD1), nucleotide-binding oligomerization domain 2 (NOD2), and disease-resistance proteins (R-protein), most representative of which is NOD1 and NOD2 [7,8,9]. e difference between NOD1 and NOD2 is that the caspaseassociated recruitment domain (CARD) of the aminoterminal domain [10, 11]
Characteristic of NOD2 and Its Cytokine Secretion after Streptococcus pneumoniae Infection. e expressions of NOD2, IL-1β, tumor necrosis factor (TNF)-α, and IL-6 in rat brain tissues were measured by enzyme-linked immunosorbent assay (ELISA), and their characteristics of changes were compared among the five groups
Summary
Streptococcus pneumoniae is the common central nervous system infectious pathogen in clinical practice [1, 2]. e overall mortality and prognosis for survivors remain unsatisfactory regardless of the application of effective antibiotics and the promotion of effective vaccination [3, 4]. It is currently believed that pattern-recognition receptors (PRR) are expressed and maybe produce inflammatory factors initiating the brain tissue immune injury [5]. Inflammatory factors can lead to secondary immune responses, brain oedema, and BBB dysfunction. 20 members of the NOD family have been reported, such as apoptotic protease-activating factor-1 (APAF-1), nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and disease-resistance proteins (R-protein), most representative of which is NOD1 and NOD2 [7,8,9]. NOD1 and NOD2 proteins can identify peptidoglycan, but their recognition dose not overlap: the NOD2 protein can recognise GlcNAc-MurNAc tripeptide muropeptide (GM-Trilys) only in Gram-positive bacteria, except for identifying GlcNAc-MurNAc dipeptide (GM-di) [6]. We focused on NOD2 because Streptococcus pneumoniae belongs to Gram-positive bacteria
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