Role of Streptococcus sanguis and traumatic factors in Behçet's disease

Background: The pathogenicity of Behçet's disease (BD) has been associated with the offending pathogen Streptococcus sanguis. However, it is unclear that the bacterium is a true pathogen. Materials and Methods: Germ-free mice were inoculated with a clinical isolate (strain BD113-20) of S. sanguis. Mice received heat or mechanical stress on their oral tissue before the bacterial infection. Colonization, immune responses against the cell wall and synthetic peptides, and the cytokine profile were examined. Uveitogenicity of the cell wall, lipoteichoic acid (LTA), muramyl dipeptide (MDP), human hsp336-351, S. sanguis-associated peptides, and retina-associated peptides were examined. Results: S. sanguis colonized the oral cavity at 10^5-8/mL saliva. The level of colonization in mice given heat or mechanical stress was significantly higher than the other groups. These mice showed typical oral ulcers after the bacterial challenge and mild iridocyclitis. Skin lesions were spread whereas genital ulcers were rare in these groups. Significant antibody production to the selected peptides was observed in the experimental mice compared with control animals. Inflammatory cytokines such as IL-2, IL-6, IFN-g, and TNF-a were detected in oral tissue of the mice infected with S. sanguis. Evidence suggests that the association with the cell wall or with LTA can directly affect the degree of inflammation. Conclusions: S. sanguis strain BD113-20 is pathogenic for experimental mice and can be a causative agent for BD. Molecular mimic peptides can be implicated in the pathogenesis of BD. The cell wall of the bacteria shows direct ocular inflammogenicity.