Abstract
Three proteins secreted by Listeria monocytogenes facilitate escape from macrophage vacuoles: the cholesterol-dependent cytolysin listeriolysin O (LLO), a phosphoinositide-specific phospholipase C (PI-PLC) and a broad-range phospholipase C (PC-PLC). LLO and PI-PLC can activate several members of the protein kinase C (PKC) family during infection. PKCε is a novel PKC that contributes to macrophage activation, defence against bacterial infection, and phagocytosis; however, a role for PKCε in Lm infections has not been described. To study PKCε dynamics, PKCε-YFP chimeras were visualized in macrophages during Lm infection. PKCε-YFP was recruited to forming vacuoles during macrophage phagocytosis of Lm and again later to fully formed Lm vacuoles. The PKCε-YFP localization to the fully formed Lm vacuole was LLO-dependent but independent of PI-PLC or PC-PLC. PKCε-YFP recruitment often followed LLO perforation of the membrane, as indicated by localization of PKCε-YFP to Lm vacuoles after they released small fluorescent dyes into the cytoplasm. PKCε-YFP recruitment to vesicles also followed phagocytosis of LLO-containing liposomes or osmotic lysis of endocytic vesicles, indicating that vacuole perforation by LLO was the chief cause of the PKCε response. These studies implicate PKCε in a cellular mechanism for recognizing damaged membranous organelles, including the disrupted vacuoles created when Lm escapes into cytoplasm.
Highlights
Macrophages are essential for clearing Listeria monocytogenes (Lm) infections in mice (Mackaness, 1962; Adams and Hamilton, 1984; Kiderlen et al, 1984; Pamer, 2004)
Three proteins secreted by Listeria monocytogenes facilitate escape from macrophage vacuoles: the cholesterol-dependent cytolysin listeriolysin O (LLO), a phosphoinositide-specific phospholipase C (PIPLC) and a broad-range phospholipase C (PC-PLC)
PKCe is a novel protein kinase C (PKC) that contributes to macrophage activation, defence against bacterial infection, and phagocytosis; a role for PKCe in Lm infections has not been described
Summary
Macrophages are essential for clearing Listeria monocytogenes (Lm) infections in mice (Mackaness, 1962; Adams and Hamilton, 1984; Kiderlen et al, 1984; Pamer, 2004). Listeria secretes a cholesterol-dependent cytolysin (CDC), listeriolysin O (LLO), which is necessary for escape from the phagosome into the cytosol (Portnoy et al, 1988; Cossart et al, 1989; Gedde et al, 2000). Lm secretes two phospholipases C which have minor roles in escape (Smith et al, 1995): a phosphatidylinositolspecific phospholipase C (PI-PLC) and a broad-range phospholipase C (PC-PLC). In addition to their involvement in bacterial escape, LLO and the bacterial phospholipases C (PLCs) induce signalling from the phagosome (Goldfine and Wadsworth, 2002). Goldfine and colleagues identified a LLO-mediated activation of host PLC and phospholipase D following Lm infection of macrophages (Goldfine et al, 2000)
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