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A Legionella type IV effector activates the NF-[kappa]B pathway by phosphorylating the I[kappa]B family of inhibitors
- Source :
- Proceedings of the National Academy of Sciences of the United States. August 18, 2009, Vol. 106 Issue 33, p13725, 6 p.
- Publication Year :
- 2009
-
Abstract
- NF-[kappa]B is critical in innate immune defense responses against invading microbial pathogens. Legionella pneumophila infection of lung macrophages causes Legionnaire's disease with pneumonia symptoms. A set of NF-[kappa]B-controlled genes involved in inflammation and anti-apoptosis are up-regulated in macrophages upon L. pneumophila infection in a Legionella Dot/Icm type IV secretion system-dependent manner. Among [approximately equal to]100 Dot/Icm substrates screened, we identified LegK1 as the sole Legionella protein that harbors a highly potent NF-[kappa]B-stimulating activity. LegK1 does not affect MAPK and IFN pathways. Activation of the NF-[kappa]B pathway by LegK1 requires its eukaryotic-like Ser/Thr kinase activity and is independent of upstream components in the NF-[kappa]B pathway, including TRAFs, NIK, MEKK3, and TAK1. Cell-free reconstitution revealed that LegK1 stimulated NF-[kappa]B activation in the absence of IKK[alpha] and IKK[beta], and LegK1 efficiently phosphorylated I[kappa]B[alpha] on Ser-32 and Ser-36 both in vitro and in cells. LegK1 seems to mimic the host IKK as LegK1 also directly phosphorylated other I[kappa]B family of inhibitors including p100 in the noncanonical NF-[kappa]B pathway. Phosphorylation of p100 by LegK1 led to its maturation into p52. Thus, LegK1 is a bacterial effector that directly activates the host NF-[kappa]B signaling and likely plays important roles in modulating macrophage defense or inflammatory responses during L. pneumophila infection. innate immunity | Legionella pneumophila | p100 processing | Type IV secretion | bacterial pathogenesis
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 33
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.208129650