A. Mansell et al., A novel function of InIB from Listeria monocytogenes: activation of NF-kappa B in J774 macrophages, CELL MICROB, 2(2), 2000, pp. 127-136
Listeria monocytogenes causes a pro-inflammatory response on adhesion to ma
crophages. Upregulation of inflammation genes involves the transcription fa
ctor NF-kappa B. Several components of L. monocytogenes, including lipoteic
hoic acid (LTA), phospholipases and listeriolysin O (LLO), have since been
shown to mediate NF-kappa B activation. Here, we report that purified recom
binant InlB, but not internalin (InlA), is a potent activator of NF-kappa B
in the mouse macrophage-like cell line J774. Expression of InlB in Listeri
a innocua enhances its ability to activate NF-kappa B, while deletion of In
lB from L. monocytogenes marginally decreases its effect on NF-kappa B, pos
sibly because of the presence of NF-kappa B activators such as LTA and LLO.
The effect correlates with the rapid degradation of I kappa B alpha, a sus
tained degradation of I kappa B beta and increases in tumour necrosis facto
r alpha (TNF-alpha) and interleukin (IL) 6 production, two cytokines contro
lled by NF-kappa B. Using a series of anti-InlB monoclonal antibodies and d
omains of InlB, NF-kappa B 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 blo
cked by PI-3 kinase inhibitors, indicating the involvement of PI-3 kinase i
n this response. This report thus illustrates that InlB not only promotes i
nvasion, but also contributes to the macrophage pro-inflammatory response.