Sonicated Extract of Enterococcus faecalis Induces Irreversible Cell Cycle Arrest in Phytohemagglutinin-Activated Human Lymphocytes

Abstract

The purpose of this study was to examine whether the sonicated extract of Enterococcus faecalis (SEF) alters the cell cycle transition of lymphocytes and thus regulates the fate of the arrested cells. Human lymphocytes were activated by phytohemagglutinin in the presence or absence of SEF, and cell cycle was assessed by flow cytometry. Seventy-two hours after activation with phytohemagglutinin, cells were activated from G0/G1 to S (6.1%) and G2/M (3.8%) phases of the cell cycle. In contrast, pretreatment with SEF resulted in 90.5% of cells remaining in G0/G1, and cell cycle progression to the S and G2/M phases was consequently inhibited. Caspase assay demonstrated that SEF-treated cells exhibited significantly increased apoptosis (56.7%) compared with phytohemagglutinin alone (28.1%). We propose that if this irreversible cell cycle arrest induced by E. faecalis occurs in vivo, it may result in local immunosuppression and contribute to the pathogenesis of endodontic failure. Our findings that E. faecalis can inhibit lymphocyte responses may be of particular relevance to the pathogenesis of endodontic failure. Although the immunologic mechanism involved in the pathogenesis of persistent periapical lesion is not clearly defined, it is reasonable to predict that the altered immune reaction may be linked to the immunosuppressive potential of E. faecalis or other oral bacteria.