Abstract
Initiation and progression of oral infectious diseases are associated with streptococcal species. Bacterial infection induces inflammatory responses together with reactive oxygen species (ROS), often causing cell death and tissue damage in the host. In the present study, we investigated the effects of oral streptococci on cytotoxicity and ROS production in human periodontal ligament (PDL) cells. Streptococcus gordonii showed cell cytotoxicity in a dose- and time-dependent manner. The cytotoxicity might be due to apoptosis since S. gordonii increased annexin V-positive cells, and the cytotoxicity was reduced by an apoptosis inhibitor, Z-VAD-FMK. Other oral streptococci such as Streptococcus mitis, Streptococcus sanguinis, and Streptococcus sobrinus also induced apoptosis, whereas Streptococcus mutans did not. All streptococci tested except S. mutans triggered ROS production in human PDL cells. Interestingly, however, streptococci-induced apoptosis appears to be ROS-independent, as the cell death induced by S. gordonii was not recovered by the ROS inhibitor, resveratrol or n-acetylcysteine. Instead, hydrogen peroxide (H2O2) appears to be important for the cytotoxic effects of streptococci since most oral streptococci except S. mutans generated H2O2, and the cytotoxicity was dramatically reduced by catalase. Furthermore, streptococcal lipoproteins are involved in cytotoxicity, as we observed that cytotoxicity induced by the lipoprotein-deficient S. gordonii mutant was less potent than that by the wild-type and was attenuated by anti-TLR2-neutralizing antibody. Indeed, lipoproteins purified from S. gordonii alone were sufficient to induce cytotoxicity. Notably, S. gordonii lipoproteins did not induce H2O2 or ROS but cooperatively induced cell death when co-treated with H2O2. Taken together, these results suggest that most oral streptococci except S. mutans efficiently induce damage to human PDL cells by inducing apoptotic cell death with bacterial H2O2 and lipoproteins, which might contribute to the progression of oral infectious diseases such as apical periodontitis.
Highlights
Streptococci are commensal Gram-positive aerobic bacteria found in human body such as skin, oral cavity, and intestine (Abranches et al, 2018)
These results suggest that S. gordonii induces damage in human periodontal ligament (PDL) cells to result in cell death
Since PDL cells play critical roles in the support of teeth in the alveolar bone (Jonsson et al, 2011), damage to PDL cells might contribute to the pathogenesis of apical periodontitis
Summary
Streptococci are commensal Gram-positive aerobic bacteria found in human body such as skin, oral cavity, and intestine (Abranches et al, 2018). Oral streptococci including S. gordonii, S. mutans, S. mitis, and S. sanguinis are commonly found in the human oral cavity (Abranches et al, 2018). They have been demonstrated to cause systemic diseases such as bacteremia, sepsis, and infective endocarditis (Park et al, 2020). As early colonizers of the oral cavity, have been isolated from infected root canals of patients with apical periodontitis (Chavez de Paz et al, 2005) and are known to cause inflammation and tissue destruction in periapical lesions (Kutlu et al, 2003). We previously reported that S. gordonii efficiently produces nitric oxide and proinflammatory cytokines in macrophages and induces bone destruction by stimulating osteoclastogenesis while inhibiting osteoblastogenesis (Kim et al, 2017b, 2018; Park et al, 2019)
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