Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection

Nair, Vidhya R.; Franco, Luis H.; Zacharia, Vineetha M.; Khan, Haaris; Stamm, Chelsea E.; You, Wei; Marciano, Denise K.; Yagita, Hideo; Levine, Beth; Shiloh, Michael U.

doi:10.1016/j.celrep.2016.06.080

Cited by 64 publications

(65 citation statements)

References 31 publications

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“…RANK-dependent GP2 + M cells have been described in the epithelium of the nasal associated lymphoid tissue (NALT) [44, 45]. The abundance of GP2 + M cells in the NALT was unaffected in RANK ΔIEC mice (Fig 1E), highlighting the intestinal specificity of the model.…”

Section: Resultsmentioning

confidence: 83%

“…Further studies are necessary to determine whether most orally acquired prion strains similarly exploit intestinal M cells to establish host infection after oral exposure, but data from independent in vivo and in vitro studies using mouse-passaged RML scrapie prions [30], Fukuoka-1 prions [31], BSE prions [32] and 263K hamster prions [17] imply a similar requirement. Antigen sampling M cells are also present in the FAE overlying the NALT in the nasal cavity [44, 45], but data from the analysis of prion disease pathogenesis in hamsters implies that the requirement for M cell-mediated uptake may vary depending on the route of exposure [85]. 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].…”

Section: Discussionmentioning

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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Section: Resultsmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…In the intestine, two cell types of the epithelium have been considered as targets for trans‐epithelial delivery: M cells and enterocytes. It is widely accepted that M cells can serve as portals for particles to cross the epithelium, perhaps with the best examples coming from microbial pathogenesis . For example, Salmonella typhimurium interactions with the epithelium can occur through GP2, a protein expressed on M cells .…”

Section: Mucosal Immunology: Considerations For Material‐based Vaccinmentioning

confidence: 99%

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

et al. 2019

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Cancer of mucosal tissues is a major cause of worldwide mortality for which only palliative treatments are available for patients with late‐stage disease. Engineered cancer vaccines offer a promising approach for inducing antitumor immunity. The route of vaccination plays a major role in dictating the migratory pattern of lymphocytes, and thus vaccine efficacy in mucosal tissues. Parenteral immunization, specifically subcutaneous and intramuscular, is the most common vaccination route. However, this induces marginal mucosal protection in the absence of tissue‐specific imprinting signals. To circumvent this, the mucosal route can be utilized, however degradative mucosal barriers must be overcome. Hence, vaccine administration route and selection of materials able to surmount transport barriers are important considerations in mucosal cancer vaccine design. Here, an overview of mucosal immunity in the context of cancer and mucosal cancer clinical trials is provided. Key considerations are described regarding the design of biomaterial‐based vaccines that will afford antitumor immune protection at mucosal surfaces, despite limited knowledge surrounding mucosal vaccination, particularly aided by biomaterials and mechanistic immune–material interactions. Finally, an outlook is given of how future biomaterial‐based mucosal cancer vaccines will be shaped by new discoveries in mucosal vaccinology, tumor immunology, immuno‐therapeutic screens, and material–immune system interplay.

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“…Although built for clearance, this first IP can also be exploited by M.tb as a portal of entry to the lymphoid tissue [18,19]. Indeed, bronchial Microfold (M) cells have been shown to translocate M.tb from the mucosa, enabling dissemination to the lymphatics [19,20].…”

Section: Mtb Transit Through the Respiratory Systemmentioning

confidence: 99%

“…Indeed, bronchial Microfold (M) cells have been shown to translocate M.tb from the mucosa, enabling dissemination to the lymphatics [19,20]. Thus M cells, located in the nasal and bronchus-associated lymphoid tissue (NALT/BALT) [19,21], are positioned to participate in generating an early protective immune response against M.tb infection [19,20]. …”

Section: Mtb Transit Through the Respiratory Systemmentioning

confidence: 99%

Integrating Lung Physiology, Immunology, and Tuberculosis

Torrelles

Schlesinger

2017

Trends in Microbiology

109

101

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Lungs are directly exposed to the air, have enormous surface area and enable gas exchange in air-breathing animals. They are constantly “attacked” by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several ‘interaction points (IPs)’ which it must overcome to cause infection. These interactions are critical, not only from a pathogenesis perspective but also in considering the effectiveness of therapies and vaccines in the lungs. Here we discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence.

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Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection

Cited by 64 publications

References 31 publications

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

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

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

Integrating Lung Physiology, Immunology, and Tuberculosis

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