Involvement of mitogen-activated protein kinases in Group B Streptococcus-induced macrophage apoptosis

We previously demonstrated that Group B Streptococcus (GBS). a pathogen that causes serious neonatal infections. induces macrophage apoptosis by beta-hemolysin to avoid the host immune response, GBS-induced macrophage apoptosis is characterized by a calcium increase and is caspase-independent. This Study reports the involvement of c-Jun NH2-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (ERK), three members of mitogen-activated protein kinases (MAPKs) family, in GBS-induced macrophage apoptosis. Our data indicate that during induction of apoptosis live GBS stimulates a strong persistent activation of JNK and p38 with concomitant inhibition of ERK. The time courses of MAPKs activation strongly correlate with GBS-induced macrophage apoptosis and are macrophage:GBS ratio-dependent. In fact, when GBS does not cause macrophage apoptosis. e.g. low macrophage:GBS ratio or non hemolytic GBS (gGBS). it induces a transient activation of JNK. p38. and ERK MAPKs. These latter results indicate that sustained and persistent activation of JNK and p38 and inhibition of ERK are involved in the GBS-induced macrophage apoptotic process and suggest that the time course and balance of MAPKs activation are critical for different macrophage responses to GBS (apoptosis versus antimicrobicidal activity). This study indicates a correlation between MAPKs activation and GBS-induced macrophage apoptosis. However. since neither ERK nor p38 inhibitors had an effect on GBS-induced apoptosis. their role in the complex signal network leading to GBS-induced macrophage apoptosis remains to be defined. (C) 2003 Elsevier Science Ltd. All rights reserved.