The type III secretion effector NleE inhibits NF-kB activation (PLoS Pathogen, 2010, 6(1):e1000743)

報告日期: 2011/03/01
報告時間: 17:10/18:00
報告學生: 黃文俊 (英文報告)
講評老師: 吳俊忠

Full test:

The Type III Secretion Effector NleE Inhibits NF-kB Activation
Chen Nadler, Kobi Baruch, Simi Kobi, Erez Mills, Gili Haviv, Marganit Farago, Irit Alkalay, Sina
Bartfeld, Thomas F. Meyer, Yinon Ben-Neriah, Ilan Rosenshine
PLoS Pathogen, 2010, 6(1):e1000743
Presenter: Wen-Chun Huang
Commentator:Jiunn-Jong Wu, Ph.D.
Date: 2011/3/1, 17:10-18:00
Place: Room 601, College of medicine
As a critical step during colonization and pathogenesis, Enteropathogenic Escherichia coli (EPEC) attach mucosa and efface microvilli on the surface of intestinal epithelial cells. In this process, EPEC express type III secretion system (TTSS) that injects effector proteins into host cells to modulate the functions to benefit bacteria.
Upon infection, toll-like receptors (TLRs) that recognized pathogen associated molecular patterns (PAMPs) on the cell surface initiate signal transduction, activate the NF-kB pathway and lead to the production of inflammatory cytokine IL-8. However, some reports showed that EPEC actually inhibit NF-kB activation by a TTSS-dependent mechanism. Up to now, the putative effector protein that presumably represses NF-kB activation has not been identified.
   In this paper, the western blotting assay showed that EPEC inhibit IκB degradation to prevent NF-κB activation by TTSS-dependent mechanism. The authors bioinformaticly compared the genome of EPEC to that of nonpathogenic E. coli K12 and identified two effector proteins (NleE and NleB) that were required for stabilizing IκB. Moreover, the authors also showed that NleB was able to enhance NleE activity. NleE inhibited TNFα- or EPEC-induced NF-κB translocation to the nucleus via inhibition of IκB phosphorylation. In addition, NleE was also required for inhibition of TNFα- or EPEC-induced IL-8 expression. Previous studies showed that both TNFα receptor and IL1/TLR receptors converged at the level of IKKβ activation by TAK1. IKKβ then phosphorylates IκB. Finally, the authors showed that NleE blocked the phosphorylation of IKKβ.


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2.     Newton HJ, Pearson JS, Badea L, Kelly M, Lucas M, et al. (2010) The Type III Effectors NleE and NleB from Enteropathogenic E. coli and OspZ from Shigella Block Nuclear Translocation of NF-kB p65. PLoS Pathog 6(5): e1000898.