A novel function of InIB from Listeria monocytogenes: activation of NF-kappaB in J774 macrophages.
Listeria monocytogenes causes a pro-inflammatory response on adhesion to macrophages. Upregulation of inflammation genes involves the transcription factor NF-kappaB. Several components of L. monocytogenes, including lipoteichoic acid (LTA), phospholipases and listeriolysin O (LLO), have since been shown to mediate NF-kappaB activation. Here, we report that purified recombinant InlB, but not internalin (InlA), is a potent activator of NF-kappaB in the mouse macrophage-like cell line J774. Expression of InlB in Listeria innocua enhances its ability to activate NF-kappaB, while deletion of InlB from L. monocytogenes marginally decreases its effect on NF-kappaB, possibly because of the presence of NF-kappaB activators such as LTA and LLO. The effect correlates with the rapid degradation of IkappaBalpha, a sustained degradation of IkappaBbeta and increases in tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 production, two cytokines controlled by NF-kappaB. Using a series of anti-InlB monoclonal antibodies and domains of InlB, NF-kappaB activation was shown to be dependent upon the N-terminal 213-amino-acid leucine-rich repeat (LRR) domain of InlB, recently demonstrated to be responsible for InlB-mediated L. monocytogenes invasion and phosphoinositide-3 (PI-3) kinase activation. The effect of InlB was blocked by PI-3 kinase inhibitors, indicating the involvement of PI-3 kinase in this response. This report thus illustrates that InlB not only promotes invasion, but also contributes to the macrophage pro-inflammatory response.
Mansell
A
A
Department of Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland.
Braun
L
L
Cossart
P
P
O'Neill
L A
LA
D000818:Animals; D001426:Bacterial Proteins; D002460:Cell Line; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008089:Listeria monocytogenes / Q000472:pathogenicity* / Q000502:physiology; D008088:Listeriosis / Q000382:microbiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014774:Virulence
D001426:Bacterial Proteins; D015850:Interleukin-6; D008565:Membrane Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C095768:inlB protein, Listeria monocytogenes; D019869:Phosphatidylinositol 3-Kinases