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Infection and Immunity, August 2002, p. 4650-4660, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4650-4660.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mobilization of Protein Kinase C in Macrophages Induced by Listeria monocytogenes Affects Its Internalization and Escape from the Phagosome

Sandra J. Wadsworth,{dagger} and Howard Goldfine*

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076

Received 26 December 2001/ Returned for modification 11 March 2002/ Accepted 19 April 2002

Listeriolysin O (LLO) and a phosphatidylinositol-specific phospholipase C (PI-PLC) are known virulence factors of Listeria monocytogenes in both tissue cultures and the murine model of infection. LLO is a member of a family of pore-forming cholesterol-dependent cytotoxins and is known to play an essential role in escape from the primary phagocytic vacuole of macrophages. PI-PLC plays an accessory role, in that PI-PLC mutants are partially defective in escape. We have shown that both of these molecules are essential for initiating rapid increases in the calcium level in the J774 murine macrophage cell line (S. J. Wadsworth and H. Goldfine, Infect. Immun. 67:1770-1778, 1999). Here we show that both LLO and PI-PLC are required for translocation of protein kinase C {delta} (PKC {delta}) to the periphery of J774 cells and for translocation of PKC ß II to early endosomes beginning within the first minute after addition of bacteria to the culture medium. Treatment with the calcium channel blocker SK&F 96365 inhibited translocation of PKC ß II but not PKC {delta}. Our findings lead us to propose a host signaling pathway requiring LLO and the formation of diacylglycerol by PI-PLC in which calcium-independent PKC {delta} is responsible for the initial calcium signal and the subsequent PKC ß II translocation. LLO-dependent translocation of PKC ß I to early endosomes also occurs between 1 and 4 min after infection, but this occurs in the absence of PI-PLC. All of these signals were observed in cells that had not internalized bacteria. Blocking PKC ß translocation with hispidin resulted in more rapid uptake of wild-type bacteria and greatly reduced escape from the primary phagocytic vacuoles of J774 cells.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076. Phone: (215) 898-6384. Fax: (215) 898-9557. E-mail: goldfinh{at}mail.med.upenn.edu.

Editor: E. I. Tuomanen

{dagger} Present address: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140-5104.

Infection and Immunity, August 2002, p. 4650-4660, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4650-4660.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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