Journal
JOURNAL OF CELL SCIENCE
Volume 118, Issue 24, Pages 5785-5796Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02709
Keywords
Toxoplasma gondii; IKK; I kappa B; NF-kappa B
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Funding
- NIAID NIH HHS [R0-1 AI49367, F32 AI056970-01] Funding Source: Medline
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Activation of NF-kappa B by the intracellular pathogen Toxoplasma gondii is associated with the localization of phosphorylated I kappa B alpha to the parasitophorous vacuole membrane (PVM). This is mediated by a parasite-derived I kappa B kinase (TgIKK) activity and is independent of host IKK function. In the present study, we examined the roles of host IKK and parasite-derived TgIKK on the temporal modulation of NF-kappa B activation. Despite the presence of TgIKK activity at the PVM, nuclear translocation of NF-kappa B and subsequent gene expression exhibited a requirement for the host IKK complex. A detailed kinetic analysis of NF-kappa B activation revealed a biphasic, hierarchical and temporally regulated response. We propose a novel paradigm for the modulation of NF-kappa B-dependent gene expression by T gondii that involves both the host IKK complex and TgIKK activity at different phases of infection. Thus, T gondii effectively alters gene expression in a temporal dimension by exploiting the NF-kappa B signaling machinery and subsequently rewiring the activation circuits of the infected host cell.
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