GROUP-B STREPTOCOCCI PERSIST INSIDE MACROPHAGES

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In the early phase of infection, macrophages and polymorphonuclear cells (PMN) are the first immune cells that int eract with GBS. In this in vitro study, to gain insight into GBS-macro phage interaction in the absence of type-specific antibodies, we exami ned the features of GBS survival in thioglycollate-elicited murine per itoneal macrophages and the effect of GBS on the protein kinase C (PKC )-dependent transduction pathway. Our results demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH 31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly in ma crophages for up to 24 and 48 hr, respectively. However, macrophage ac tivation by interferon-gamma (IFN-gamma) and lipopolysaccharide from E scherichia coli (LPS) caused a significant reduction in the time of in tracellular persistence. Macrophage activation by IFN-gamma and LPS se ems to be a multifactorial event involving multiple intracellular sign al pathways also including PKC. Since PKC is one of the components in the signal network leading to macrophage activation and an important t arget for several intracellular micro-organisms, we wondered whether P KC could have a role in intracellular GBS survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate (PMA) for 18 kr and PKC inhibition by Calphostin C rendered macrophages more permissive f or the intracellular GBS survival. Furthermore, GBS-infected macrophag es were unable to respond to PMA and LPS, activators of PKC, by induci ng antimicrobial activity. The ability of GBS to impair PKC-dependent cell signalling was also demonstrated by the reduced c-fos gene expres sion in GBS-infected macrophages with respect to control macrophages, after LPS stimulation. In conclusion, our results indicate that GBS su rvive in macrophages and impairment of PKC signal transduction contrib utes to their intracellular survival.