title: Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion.
abstract: Salmonella Typhimurium specifically targets antigen-sampling microfold (M) cells to translocate across the gut epithelium. Although M cells represent a small proportion of the specialized follicular-associated epithelium (FAE) overlying mucosa-associated lymphoid tissues, their density increases during Salmonella infection, but the underlying molecular mechanism remains unclear. Using in vitro and in vivo infection models, we demonstrate that the S. Typhimurium type III effector protein SopB induces an epithelial-mesenchymal transition (EMT) of FAE enterocytes into M cells. This cellular transdifferentiation is a result of SopB-dependent activation of Wnt/β-catenin signaling leading to induction of both receptor activator of NF-κB ligand (RANKL) and its receptor RANK. The autocrine activation of RelB-expressing FAE enterocytes by RANKL/RANK induces the EMT-regulating transcription factor Slug that marks epithelial transdifferentiation into M cells. Thus, via the activity of a single secreted effector, S. Typhimurium transforms primed epithelial cells into M cells to promote host colonization and invasion.
authors.affiliation: The Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.
authors.forename: Amin
authors.initials: A
authors.lastname: Tahoun
authors.forename: Simmi
authors.initials: S
authors.lastname: Mahajan
authors.forename: Edith
authors.initials: E
authors.lastname: Paxton
authors.forename: Georg
authors.initials: G
authors.lastname: Malterer
authors.forename: David S
authors.initials: DS
authors.lastname: Donaldson
authors.forename: Dai
authors.initials: D
authors.lastname: Wang
authors.forename: Alwyn
authors.initials: A
authors.lastname: Tan
authors.forename: Trudi L
authors.initials: TL
authors.lastname: Gillespie
authors.forename: Marie
authors.initials: M
authors.lastname: O'Shea
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roe
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Shaw
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
authors.forename: Andreas
authors.initials: A
authors.lastname: Lengeling
authors.forename: Neil A
authors.initials: NA
authors.lastname: Mabbott
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas
authors.forename: Arvind
authors.initials: A
authors.lastname: Mahajan
mesh_terms: D000627:Aminophenols / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001596:Benzylamines / Q000494:pharmacology; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D020895:Enterocytes / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology*; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011810:Quinoxalines / Q000494:pharmacology; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D012480:Salmonella Infections / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism / Q000472:pathogenicity*; D000071250:Snail Family Transcription Factors; D051841:Transcription Factor RelB / Q000096:biosynthesis / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C417520:3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione; C501521:Akt-I-1,2 compound; D000627:Aminophenols; D001426:Bacterial Proteins; D001596:Benzylamines; D002867:Chromones; D008301:Maleimides; D009025:Morpholines; D016328:NF-kappa B; D010455:Peptides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011810:Quinoxalines; D053245:RANK Ligand; C497593:RELB protein, human; D053246:Receptor Activator of Nuclear Factor-kappa B; C118258:SN50 peptide; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; C505688:TNFSF11 protein, human; D014157:Transcription Factors; D014746:Vimentin; D051153:Wnt Proteins; D051176:beta Catenin; D051841:Transcription Factor RelB; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C489224:SopB protein, Salmonella