1. The Type III Secretion Effector NleE Inhibits NF-κB Activation
- Author
-
Erez Mills, Thomas F. Meyer, Sina Bartfeld, Kobi Baruch, Yinon Ben-Neriah, Marganit Farago, Simi Kobi, Chen Nadler, Irit Alkalay, Gili Haviv, and Ilan Rosenshine
- Subjects
lcsh:Immunologic diseases. Allergy ,Virulence Factors ,Immunology ,Blotting, Western ,Inflammation ,Microbiology/Innate Immunity ,Biology ,Transfection ,Microbiology ,Enteropathogenic Escherichia coli ,Virology ,Genetics ,medicine ,Humans ,Secretion ,lcsh:QH301-705.5 ,Molecular Biology ,Transcription factor ,Escherichia coli Infections ,Innate immune system ,Effector ,Escherichia coli Proteins ,NF-kappa B ,NFKB1 ,Enzyme Activation ,Protein Transport ,lcsh:Biology (General) ,Immunology/Immune Response ,Parasitology ,I-kappa B Proteins ,Signal transduction ,medicine.symptom ,lcsh:RC581-607 ,Research Article ,HeLa Cells ,Signal Transduction - Abstract
The complex host-pathogen interplay involves the recognition of the pathogen by the host's innate immune system and countermeasures taken by the pathogen. Detection of invading bacteria by the host leads to rapid activation of the transcription factor NF-κB, followed by inflammation and eradication of the intruders. In response, some pathogens, including enteropathogenic Escherichia coli (EPEC), acquired means of blocking NF-κB activation. We show that inhibition of NF-κB activation by EPEC involves the injection of NleE into the host cell. Importantly, we show that NleE inhibits NF-κB activation by preventing activation of IKKβ and consequently the degradation of the NF-κB inhibitor, IκB. This NleE activity is enhanced by, but is not dependent on, a second injected effector, NleB. In conclusion, this study describes two effectors, NleB and NleE, with no similarity to other known proteins, used by pathogens to manipulate NF-κB signaling pathways., Author Summary The innate immune system senses intruding pathogens and in response, mounts an inflammatory reaction. Essential for this response is the activation of the transcription factor NF-κB, which mediates reprogramming of gene expression in the host. The bacteria Escherichia coli is usually a non-pathogenic resident of our intestinal track. Some E. coli strains, however, cause disease or food poisoning; one of these pathogenic strains is enteropathogenic E. coli (EPEC). This pathogen employs a syringe-like organelle, termed type three secretion system (TTSS), to inject into the intestinal host cell a battery of toxic proteins termed effectors. We found that two of the effectors that EPEC injects into the host cell upon infection block the activation of NF-κB and thus interfere with the host immune response. These findings elucidate the intricate cross-talk between the host immune system and the pathogen.
- Published
- 2010