Hydrogen Peroxide Produced by Oral Streptococci Induces Macrophage Cell Death

Abstract

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.