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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Protein kinase C δ is essential for optimal macrophage-mediated phagosomal containment of Listeria monocytogenes
Proceedings of the National Academy of Sciences of the United States of America, Volume 104, No. 41, Year 2007
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Description
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-γ 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, PKCδ, had higher mRNA levels in the LM-infected NF-IL6-deficient macrophages as compared with WT. To define the role of PKCδ during listeriosis, we infected PKCδ-deficient mice with LM. PKCδ-deficient mice were highly susceptible to LM infection with increased bacterial burden and enhanced histopathology despite enhanced NF-IL6 mRNA expression. Subsequent studies in PKCδ-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 PKCδ as a critical factor for confinement of LM within macrophage phagosomes. © 2007 by The National Academy of Sciences of the USA.
Authors & Co-Authors
Schwegmann, Anita
South Africa, Cape Town
University of Cape Town
Guler, Reto
South Africa, Cape Town
University of Cape Town
Cutler, Antony J.
South Africa, Cape Town
University of Cape Town
Arendse, Berenice
South Africa, Cape Town
University of Cape Town
Horsnell, William Gordon Charles
South Africa, Cape Town
University of Cape Town
Flemming, Alexandra
South Africa, Cape Town
University of Cape Town
Kottmann, Andreas H.
United States, New York
Columbia University
Ryan, Gregory
United States, New York
Intra-cellular Therapies, Inc.
Hide, Winston A.
South Africa, Bellville
University of the Western Cape
Leitges, Michael
Norway, Oslo
Universitetet I Oslo
Seoighe, Cathal
South Africa, Cape Town
University of Cape Town
Brombacher, Frank
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 38
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1073/pnas.0703496104
ISSN:
00278424
Research Areas
Genetics And Genomics