Anginosus group streptococci (AGS) has historically been identified as an opportunistic pathogen inhabiting the human oral cavity. However, recent reports indicate that the species of AGS have been frequently isolated from infections and disorders beyond those in the oral cavity, suggesting their potential involvement in ectopic infections. The β-hemolytic strains of Streptococcus anginosus subsp. anginosus (SAA) produce streptolysin S (SLS), a streptococcal peptide hemolysin. Therefore, investigating the role of SLS in AGS infections is essential for revealing its potential pathogenicity. However, the precise mechanism underlying the cellular response induced by the secreted SLS and its relevance to the pathogenicity of AGS remain largely unknown. According to these situations, this study aims to elucidate the mechanism underlying the host cellular response of the human acute monocytic leukemia cell line THP-1 to secreted SLS.
In THP-1 incubated with the culture supernatant of β-hemolytic SAA containing SLS as the sole cytotoxic factor, increased Ca2+-influx and elevated expression of both proinflammatory cytokines and chemokines were observed. The SLS-dependent upregulation of cytokine-encoding genes was significantly reduced under Ca2+-chelating conditions, suggesting that Ca2+-influx triggers SLS-dependent cellular responses. Furthermore, SLS-dependent enhanced expression of cytokines was also implicated in the activation of MAPK including ERK, p38 MAPK, and JNK signaling pathways. The findings presented in this study are crucial for a comprehensive understanding of the real pathogenicity of SLS-producing β-hemolytic AGS in the present clinical situations.