Hydrogen Peroxide Produced by Oral Streptococci Induces Macrophage Cell Death

Hydrogen peroxide (H(2)O(2)) produced by members of the mitis group of oral streptococci plays important roles in microbial communities such as oral biofilms. Although the cytotoxicity of H(2)O(2) has been widely recognized, the effects of H(2)O(2) produced by oral streptococci on host defense systems remain unknown. In the present study, we investigated the effect of H(2)O(2) produced by Streptococcus oralis on human macrophage cell death. Infection by S. oralis was found to stimulate cell death of a THP-1 human macrophage cell line at multiplicities of infection greater than 100. Catalase, an enzyme that catalyzes the decomposition of H(2)O(2), inhibited the cytotoxic effect of S. oralis. S. oralis deletion mutants lacking the spxB gene, which encodes pyruvate oxidase, and are therefore deficient in H(2)O(2) production, showed reduced cytotoxicity toward THP-1 macrophages. Furthermore, H(2)O(2) alone was capable of inducing cell death. The cytotoxic effect seemed to be independent of inflammatory responses, because H(2)O(2) was not a potent stimulator of tumor necrosis factor-α production in macrophages. These results indicate that streptococcal H(2)O(2) plays a role as a cytotoxin, and is implicated in the cell death of infected human macrophages.