Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion

Amin Tahoun; Simmi Mahajan; Edith Paxton; Georg Malterer; David S Donaldson; Dai Wang; Alwyn Tan; Trudi L Gillespie; Marie O'Shea; Andrew J Roe; Darren J Shaw; David L Gally; Andreas Lengeling; Neil A Mabbott; Juergen Haas; Arvind Mahajan

doi:10.1016/j.chom.2012.10.009

Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion

Amin Tahoun, Simmi Mahajan, Edith Paxton, Georg Malterer, David S Donaldson, Dai Wang, Alwyn Tan, Trudi L Gillespie, Marie O'Shea, Andrew J Roe, Darren J Shaw, David L Gally, Andreas Lengeling, Neil A Mabbott, Juergen Haas, Arvind Mahajan

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	645-56
Number of pages	12
Journal	Cell Host & Microbe
Volume	12
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2012.10.009
Publication status	Published - 2012

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10.1016/j.chom.2012.10.009

http://www.sciencedirect.com/science/article/pii/S193131281200354X

Determining the role of m cells in tse agent neuroinvasion from the intestine
Mabbott, N. (Principal Investigator) & Mahajan, A. (Co-investigator)
BBSRC
1/11/12 → 31/03/16
Project: Research
Livestock neurobiology
Gill, A. (Principal Investigator), Barron, R. (Co-investigator), Beard, P. (Co-investigator), Brunton, P. (Co-investigator), Goldmann, W. (Co-investigator), Hume, D. (Co-investigator), Hunter, N. (Co-investigator), Lawrence, A. (Co-investigator), Mabbott, N. (Co-investigator), Manson, J. (Co-investigator), McColl, B. (Co-investigator), Meddle, S. (Co-investigator) & Wishart, T. (Co-investigator)
BBSRC
1/04/12 → 31/03/17
Project: Research
Innate immunity and endemic diseases in livestock species
Collie, D. (Principal Investigator), Beard, P. (Co-investigator), Bishop, S. (Co-investigator), Bronsvoort, M. (Co-investigator), Burt, D. (Co-investigator), Fitzgerald, R. (Co-investigator), Freeman, T. (Co-investigator), Gally, D. (Co-investigator), Gill, A. (Co-investigator), Glass, E. (Co-investigator), Hocking, P. (Co-investigator), Hope, J. (Co-investigator), Hume, D. (Co-investigator), Kaiser, P. (Co-investigator), Mabbott, N. (Co-investigator), McLachlan, G. (Co-investigator), Morrison, L. (Co-investigator), Stevens, J. (Co-investigator), Stevens, M. (Co-investigator) & Watson, M. (Co-investigator)
BBSRC
1/04/12 → 31/03/17
Project: Research

Cite this

Tahoun, A., Mahajan, S., Paxton, E., Malterer, G., Donaldson, D. S., Wang, D., Tan, A., Gillespie, T. L., O'Shea, M., Roe, A. J., Shaw, D. J., Gally, D. L., Lengeling, A., Mabbott, N. A., Haas, J., & Mahajan, A. (2012). Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion. Cell Host & Microbe, 12(5), 645-56. https://doi.org/10.1016/j.chom.2012.10.009

@article{1b71bcc71eaa40fdaac6d94ee5cc6dd4,

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.",

author = "Amin Tahoun and Simmi Mahajan and Edith Paxton and Georg Malterer and Donaldson, {David S} and Dai Wang and Alwyn Tan and Gillespie, {Trudi L} and Marie O'Shea and Roe, {Andrew J} and Shaw, {Darren J} and Gally, {David L} and Andreas Lengeling and Mabbott, {Neil A} and Juergen Haas and Arvind Mahajan",

year = "2012",

doi = "10.1016/j.chom.2012.10.009",

language = "English",

volume = "12",

pages = "645--56",

journal = "Cell Host & Microbe",

issn = "1934-6069",

publisher = "Cell Press",

number = "5",

}

Tahoun, A, Mahajan, S, Paxton, E, Malterer, G, Donaldson, DS, Wang, D, Tan, A, Gillespie, TL, O'Shea, M, Roe, AJ, Shaw, DJ , Gally, DL, Lengeling, A, Mabbott, NA , Haas, J & Mahajan, A 2012, 'Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion', Cell Host & Microbe, vol. 12, no. 5, pp. 645-56. https://doi.org/10.1016/j.chom.2012.10.009

TY - JOUR

T1 - Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion

AU - Tahoun, Amin

AU - Mahajan, Simmi

AU - Paxton, Edith

AU - Malterer, Georg

AU - Donaldson, David S

AU - Wang, Dai

AU - Tan, Alwyn

AU - Gillespie, Trudi L

AU - O'Shea, Marie

AU - Roe, Andrew J

AU - Shaw, Darren J

AU - Gally, David L

AU - Lengeling, Andreas

AU - Mabbott, Neil A

AU - Haas, Juergen

AU - Mahajan, Arvind

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1016/j.chom.2012.10.009

DO - 10.1016/j.chom.2012.10.009

M3 - Article

C2 - 23159054

SN - 1934-6069

VL - 12

SP - 645

EP - 656

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 5

ER -

Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion

Abstract

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Projects

Determining the role of m cells in tse agent neuroinvasion from the intestine

Livestock neurobiology

Innate immunity and endemic diseases in livestock species

Cite this