Listeria monocytogenes infection of P388D1 macrophages results in a biphasic NF-kappaB (RelA/p50) activation induced by lipoteichoic acid and bacterial phospholipases and mediated by IkappaBalpha and IkappaBbeta degradation.
As previously reported, Listeria monocytogenes infection of P388D1 macrophages results in a rapid induction of NF-kappaB DNA-binding activity. Here we show that this induction of NF-kappaB activity occurs in a biphasic mode: first, a transient, IkappaBalpha degradation-dependent phase of activity, also induced by the nonvirulent species Listeria innocua, which is mediated by binding of the bacteria to the macrophage, or by adding Listeria-derived lipoteichoic acid to the macrophage; the second persistent phase of activation is only markedly induced when the bacteria enter the cytoplasm of the host cell and express the virulence genes plcA and plcB, encoding two phospholipases. We suggest that products of the enzymatic activity of phospholipases directly interfere with host cell signal transduction pathways, thus leading to persistent NF-kappaB activation via persistent IkappaBbeta degradation.
Hauf
N
N
Theodor Boveri Institut für Biowissenschaften, Lehrstuhl für Mikrobiologie, Am Hubland, 97074 Würzburg, Germany.
Goebel
W
W
Fiedler
F
F
Sokolovic
Z
Z
Kuhn
M
M
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D007941:Leukemia P388 / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010740:Phospholipases / Q000494:pharmacology*; D013682:Teichoic Acids / Q000494:pharmacology*
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D013682:Teichoic Acids; D000072000:NF-KappaB Inhibitor alpha; C009900:lipoteichoic acid; D010740:Phospholipases