Epithelial cells detect functional type III secretion system of enteropathogenic Escherichia coli through a novel NF-κB signaling pathway

Yael Litvak, Shir Sharon, Meirav Hyams, Li Zhang, Simi Kobi, Naama Katsowich, Shira Dishon, Gabriel Nussbaum, Na Dong, Feng Shao, Ilan Rosenshine*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Enteropathogenic Escherichia coli (EPEC), a common cause of infant diarrhea, is associated with high risk of mortality in developing countries. The primary niche of infecting EPEC is the apical surface of intestinal epithelial cells. EPEC employs a type three secretion system (TTSS) to inject the host cells with dozens of effector proteins, which facilitate attachment to these cells and successful colonization. Here we show that EPEC elicit strong NF-κB activation in infected host cells. Furthermore, the data indicate that active, pore-forming TTSS per se is necessary and sufficient for this NF-κB activation, regardless of any specific effector or protein translocation. Importantly, upon infection with wild type EPEC this NF-κB activation is antagonized by anti-NF-κB effectors, including NleB, NleC and NleE. Accordingly, this NF-κB activation is evident only in cells infected with EPEC mutants deleted of nleB, nleC, and nleE. The TTSS-dependent NF-κB activation involves a unique pathway, which is independent of TLRs and Nod1/2 and converges with other pathways at the level of TAK1 activation. Taken together, our results imply that epithelial cells have the capacity to sense the EPEC TTSS and activate NF-κB in response. Notably, EPEC antagonizes this capacity by delivering anti-NF-κB effectors into the infected cells.

Original languageAmerican English
Article numbere1006472
JournalPLoS Pathogens
Volume13
Issue number7
DOIs
StatePublished - Jul 2017

Bibliographical note

Publisher Copyright:
© 2017 Litvak et al.

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