title: Campylobacter jejuni activates NF-kappaB independently of TLR2, TLR4, Nod1 and Nod2 receptors.
abstract: Campylobacter jejuni activates the host transcription factor NF-kappaB that regulates the expression of a number of genes involved in the inflammatory response to bacterial infection. Signaling pathways leading to NF-kappaB by pathogens and/or their products include transmembrane Toll-like receptors (TLRs) and intracellular receptors nucleotide-binding oligomerization domain proteins (Nods). This study was carried out to investigate the role of TLRs (TLR2 and TLR4) and Nods (Nod1 and Nod2) receptors in mediating NF-kappaB activation by C. jejuni. By means of transfecting receptors/molecules under study and measuring reporter gene activity, NF-kappaB activation and subsequent cytokine production by live, heat-killed C. jejuni, or boiled cell extract (BCE) were observed in a range of tissue culture cell lines. This activation is reduced upon transfection of cells with the dominant negative versions (DNV) of TLR-adaptor molecule MyD88. NF-kappaB activation was observed to be augmented in cell lines transfected with TLR2, Nod1, and Nod2 but not with TLR4. Additionally, NF-kappaB activation by C. jejuni was observed to be independent of Nod1 and Nod2 in cells transfected with DNV of these receptors. NF-kappaB activation pathway by C. jejuni may represent a novel mechanism utilising unknown receptors up-regulated by yet to be characterized active component(s). To our knowledge, such observations have not been previously reported for C. jejuni or any other food-borne pathogen.
authors.affiliation: Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraidah, Saudi Arabia. saaeg@qu.edu.sa
authors.forename: Abdullah F
authors.initials: AF
authors.lastname: Al-Sayeqh
authors.forename: Michael F
authors.initials: MF
authors.lastname: Loughlin
authors.forename: Eleanor
authors.initials: E
authors.lastname: Dillon
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mellits
authors.forename: Ian F
authors.initials: IF
authors.lastname: Connerton
mesh_terms: D016123:Campylobacter jejuni / Q000276:immunology* / Q000472:pathogenicity*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4