Previous Article |
Table of Contents
| Next Article 
BIOLOGICAL SCIENCES / IMMUNOLOGY
Protein kinase C 
is essential for optimal macrophage-mediated phagosomal containment of Listeria monocytogenes
*Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, and ||National Bioinformatics Network Node, University of Cape Town, Cape Town 7925, South Africa; Psychogenics Inc., Genome Center, and Department of Psychiatry, Columbia University, New York, NY 10032; Intracellular Therapies, Inc., New York, NY 10032; South African National Bioinformatics Institute, University of Western Cape, Bellville 7535, South Africa; and ¶Biotechnology Centre of Oslo, University of Oslo, 0317 Oslo, Norway
Edited by Emil R. Unanue, Washington University School of Medicine, St. Louis, MO, and approved August 20, 2007 (received for review April 16, 2007)
Activation of macrophages and subsequent "killing" effector functions against infectious pathogens are essential for the establishment of protective immunity. NF-IL6 is a transcription factor downstream of IFN-
and TNF in the macrophage activation pathway required for bacterial killing. Comparison of microarray expression profiles of Listeria monocytogenes (LM)-infected macrophages from WT and NF-IL6-deficient mice enabled us to identify candidate genes downstream of NF-IL6 involved in the unknown pathways of LM killing independent of reactive oxygen intermediates and reactive nitrogen intermediates. One differentially expressed gene, PKC
, had higher mRNA levels in the LM-infected NF-IL6-deficient macrophages as compared with WT. To define the role of PKC during listeriosis, we infected PKC-deficient mice with LM. PKC-deficient mice were highly susceptible to LM infection with increased bacterial burden and enhanced histopathology despite enhanced NF-IL6 mRNA expression. Subsequent studies in PKC-deficient macrophages demonstrated that, despite elevated levels of proinflammatory cytokines and NO production, increased escape of LM from the phagosome into the cytoplasm and uncontrolled bacterial growth occurred. Taken together these data identified PKC as a critical factor for confinement of LM within macrophage phagosomes.
microarray | phagosomal escape | bacterial killing
Author contributions: A.S. and R.G. contributed equally to this work; A.S., R.G., C.S., and F.B. designed research; A.S., R.G., A.J.C., B.A., W.G.C.H., A.F., and G.R. performed research; A.H.K., W.H., M.L., and F.B. contributed new reagents/analytic tools; A.S., R.G., A.J.C., and C.S. analyzed data; and A.S. and R.G. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE6256).
**To whom correspondence should be addressed at: Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Anzio Road, Observatory, Cape Town 7925, South Africa. E-mail: fbrombac{at}mweb.co.za
© 2007 by The National Academy of Sciences of the USA
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
