Induction of Colonic M Cells during Intestinal Inflammation

Bennett, Kaila M.; Parnell, Erinn; Sanscartier, Candice April; Parks, Sophia C.; Chen, Gang; Nair, Meera G.; Lo, David

doi:10.1016/j.ajpath.2015.12.015

Cited by 45 publications

(40 citation statements)

References 49 publications

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“…After intra-nasal exposure some transient uptake of 263K prions was observed in M cells within the FAE overlying the NALT, but a greater magnitude of paracellular transport across the epithelia within the nasal cavity was also noted [85]. Although certain concurrent pathogen infections, inflammatory stimuli and aging may have multiple effects on the gut epithelium, our data suggest that factors such as these that can modify M cell-density in the small intestine [25, 39, 40, 71] may represent important risk factors which can significantly influence susceptibility to orally-acquired prion infections. Our data also raise the possibility that the density of M cells in the gut epithelium may similarly influence susceptibility to other important orally-acquired bacterial and viral pathogens which are considered to exploit M cells to infect the host [24–28].…”

Section: Discussionmentioning

confidence: 86%

“…The density of M cells in the gut epithelium can be modified by the presence of certain pathogenic bacteria or inflammatory stimuli [25, 39, 40]. Although these stimuli may have multiple effects on the gut epithelium which can influence the integrity of this barrier, data in the current study provide a significant advance in our understanding of how factors that increase the density of M cells in the gut epithelium may increase susceptibility to orally-acquired prion infection.…”

Section: Discussionmentioning

confidence: 88%

“…Together, these data demonstrate that increased M cell-deficiency in the gut epithelium following RANKL-treatment significantly enhances oral prion disease susceptibility by approximately 10-fold. Although certain concurrent pathogen infections or inflammatory stimuli may have multiple effects on the gut epithelium, our data suggest that factors such as these that modify M cell-density in the intestine [25, 39, 40] may represent important risk factors which can significantly influence susceptibility to orally-acquired prion infections.…”

Section: Resultsmentioning

confidence: 98%

“…Certain pathogen infections or inflammatory conditions can enhance M cell-differentiation within the intestine [25, 39, 40]. We therefore reasoned that alterations to M cell-density in the gut epithelium may significantly alter oral prion disease pathogenesis and susceptibility.…”

Section: Resultsmentioning

confidence: 99%

“…Certain pathogenic bacteria [25, 39] or exposure to inflammatory stimuli such as cholera toxin [40] can significantly increase the density of M cells in the intestine. Inflammation or pathogen infection can also influence prion disease pathogenesis by enhancing the uptake, or expanding the distribution, of prions within the host [11, 41–43].…”

Section: Introductionmentioning

confidence: 99%

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Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility

et al. 2016

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Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer’s patches is essential for the efficient spread of disease to the brain. To replicate within Peyer’s patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer’s patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer’s patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases.

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