Listeria monocytogenes infection of P388D 1 macrophages results in a biphasic NF-κB (RelA/p50) activation induced by lipoteichoic acid and bacterial phospholipases and mediated by IκBα and IκBβ degradation

As previously reported,Listeria monocytogenes infection of P388D1 macrophages results in a rapid induction of NF-κB DNA-binding activity. Here we show that this induction of NF-κB activity occurs in a biphasic mode: first, a transient, IκBα degradation-dependent phase of activity, also induced by the nonvirulent speciesListeria innocua , which is mediated by binding of the bacteria to the macrophage, or by addingListeria -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 genesplcA andplcB, 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-κB activation via persistent IκBβ degradation.