Faculty Opinions recommendation of Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion.

2012 ◽  
Author(s):  
Steven R Blanke
Keyword(s):  
Epithelial Cells ◽  
M Cells

scholarly journals Comparative Analysis of EspF Variants in Inhibition of Escherichia coli Phagocytosis by Macrophages and Inhibition of E. coli Translocation through Human- and Bovine-Derived M Cells

2011 ◽  
Vol 79 (11) ◽  
pp. 4716-4729 ◽  
Author(s):  
Amin Tahoun ◽  
Gabriella Siszler ◽  
Kevin Spears ◽  
Sean McAteer ◽  
Jai Tree ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Cellular Localization ◽  
M Cells ◽  
Binding Assays ◽  
M Cell ◽  
Content Type ◽  
E Coli ◽  
Coculture System

ABSTRACTThe EspF protein is secreted by the type III secretion system of enteropathogenic and enterohemorrhagicEscherichia coli(EPEC and EHEC, respectively). EspF sequences differ between EHEC O157:H7, EHEC O26:H11, and EPEC O127:H6 in terms of the number of SH3-binding polyproline-rich repeats and specific residues in these regions, as well as residues in the amino domain involved in cellular localization. EspFO127is important for the inhibition of phagocytosis by EPEC and also limits EPEC translocation through antigen-sampling cells (M cells). EspFO127has been shown to have effects on cellular organelle function and interacts with several host proteins, including N-WASP and sorting nexin 9 (SNX9). In this study, we compared the capacities of differentespFalleles to inhibit (i) bacterial phagocytosis by macrophages, (ii) translocation through an M-cell coculture system, and (iii) uptake by and translocation through cultured bovine epithelial cells. TheespFgene fromE. coliserotype O157 (espFO157) allele was significantly less effective at inhibiting phagocytosis and also had reduced capacity to inhibitE. colitranslocation through a human-derivedin vitroM-cell coculture system in comparison toespFO127andespFO26. In contrast,espFO157was the most effective allele at restricting bacterial uptake into and translocation through primary epithelial cells cultured from the bovine terminal rectum, the predominant colonization site of EHEC O157 in cattle and a site containing M-like cells. Although LUMIER binding assays demonstrated differences in the interactions of the EspF variants with SNX9 and N-WASP, we propose that other, as-yet-uncharacterized interactions contribute to the host-based variation in EspF activity demonstrated here.

scholarly journals Identifying human and murine M cells in vitro

2019 ◽  
Vol 244 (7) ◽  
pp. 554-564 ◽  
Author(s):  
Ana Klisuric ◽  
Benjamin Thierry ◽  
Ludivine Delon ◽  
Clive A Prestidge ◽  
Rachel J Gibson
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
In Vitro Models ◽  
Oral Drug ◽  
M Cells ◽  
Cell Marker ◽  
M Cell ◽  
Follicle Associated Epithelium

M cells are an epithelial cell population found in the follicle-associated epithelium overlying gut-associated lymphoid tissues. They are specialized in the transcytosis of luminal antigens. Their transcytotic capacity and location in an immunocompetent environment has prompted the study of these cells as possible targets for oral drug delivery systems. Currently, the models most commonly used to study M cells are restricted to in vivo experiments conducted in mice, and in vitro studies conducted in models comprised either of primary epithelial cells or established cell lines of murine or human origin. In vitro models of the follicle-associated epithelium can be constructed in several ways. Small intestinal Lgr5+ stem cells can be cultured into a 3D organoid structure where M cells are induced with RANKL administration. Additionally, in vitro models containing an “M cell-like” population can be obtained through co-culturing intestinal epithelial cells with cells of lymphocytic origin to induce the M cell phenotype. The evaluation of the efficiency of the variations of these models and their relevance to the in vivo human system is hampered by the lack of a universal M cell marker. This issue has also hindered the advancement of M cell-specific targeting approaches aimed at improving the bioavailability of orally administered compounds. This critical review discusses the different approaches utilized in the literature to identify M cells, their efficiency, reliability and relevance, in the context of commonly used models of the follicle-associated epithelium. The outcome of this review is a clearly defined and universally recognized criteria for the assessment of the relevance of models of the follicle-associated models currently used. Impact statement The study of M cells, a specialized epithelial cell type found in the follicle-associated epithelium, is hampered by the lack of a universal M cell marker. As such, many studies lack reliable and universally recognized methods to identify M cells in their proposed models. As a result of this it is difficult to ascertain whether the effects observed are due to the presence of M cells or an unaccounted variable. The outcome of this review is the thorough evaluation of the many M cell markers that have been used in the literature thus far and a proposed criterion for the identification of M cells for future publications. This will hopefully lead to an improvement in the quality of future publications in this field.

scholarly journals M-cells in the rabbit tonsil exhibit distinctive glycoconjugates in their apical membranes.

1996 ◽  
Vol 44 (9) ◽  
pp. 1033-1042 ◽  
Author(s):  
A Gebert
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Cell Types ◽  
Lectin Histochemistry ◽  
Lymphoid Cells ◽  
M Cells ◽  
M Cell ◽  
Double Labeling ◽  
Specific Composition ◽  
Apical Membranes

The tonsil crypt epithelium contains membranous (M)-cells that transport antigens from the lumen to underlying lymphoid cells, thereby initiating specific immune responses. Mechanisms mediating the adhesion of antigens to the M-cell surface are important for effective and selective uptake of potential pathogens but are still poorly understood. Therefore, the carbohydrates present on crypt epithelial cells of the rabbit palatine tonsil were studied by lectin histochemistry. Ultrathin LR White sections were incubated with a panel of eight lectins conjugated to colloidal gold or biotin. The glycocalyx of the apical membrane of M-cells was selectively labeled by UEA-I, LTA, HPA, and VVA, whereas that of the remaining squamous epithelial cells preferentially bound RCA-I and PNA. WGA and ConA showed only little binding, with no discernible preference for any of the cell types. Double labeling of UEA-1 together with anti-vimentin antibodies revealed that UEA-I-positive epithelial cells also contained the rabbit M-cell marker vimentin, and vice versa. The results show that a specific composition of glycoconjugates, which differs from that on squamous epithelial cells, is found on M-cells of the rabbit tonsil. The M-cell-specific glycoproteins and glycolipids could be selectively targeted by microorganisms that adhere to M-cells and enter the host along this pathway.

scholarly journals Mycobacterium avium subsp. paratuberculosis Fibronectin Attachment Protein Facilitates M-Cell Targeting and Invasion through a Fibronectin Bridge with Host Integrins

2004 ◽  
Vol 72 (7) ◽  
pp. 3724-3732 ◽  
Author(s):  
T. E. Secott ◽  
T. L. Lin ◽  
C. C. Wu
Keyword(s):  
Epithelial Cells ◽  
Mycobacterium Avium ◽  
Cell Invasion ◽  
M Cells ◽  
Intestinal Epithelial ◽  
M Cell ◽  
Attachment Protein ◽  
Β3 Integrin ◽  
Mycobacterium Avium Subsp Paratuberculosis

ABSTRACT Efficient attachment and ingestion of Mycobacterium avium subsp. paratuberculosis by cultured epithelial cells requires the expression of a fibronectin (FN) attachment protein homologue (FAP-P) which mediates FN binding by M. avium subsp. paratuberculosis. Invasion of Peyer's patches by M. avium subsp. paratuberculosis occurs through M cells, which, unlike other intestinal epithelial cells, express integrins on their luminal faces. We sought to determine if the interaction between FAP-P of M. avium subsp. paratuberculosis and soluble FN enabled targeting and invasion of M cells by M. avium subsp. paratuberculosis in vivo via these surface integrins. Wild-type and antisense FAP-P mutant M. avium subsp. paratuberculosis strains were injected alone or coinjected with blocking peptides or antibodies into murine gut loops, and immunofluorescence microscopy was performed to assess targeting and invasion of M cells by M. avium subsp. paratuberculosis. Nonopsonized M. avium subsp. paratuberculosis preferentially invaded M cells in murine gut loops. M-cell invasion was enhanced 2.6-fold when M. avium subsp. paratuberculosis was pretreated with FN. Invasion of M cells by the antisense FAP-P mutant of M. avium subsp. paratuberculosis was reduced by 77 to 90% relative to that observed for the control strains. Peptides corresponding to the RGD and synergy site integrin recognition regions of FN blocked M. avium subsp. paratuberculosis invasion of M cells by 75 and 45%, respectively, whereas the connecting segment 1 peptide was noninhibitory. Antibodies against the α5, αV, β1, and β3 integrin subunits inhibited M-cell invasion by 52 to 73%. The results indicate that targeting and invasion of M cells by M. avium subsp. paratuberculosis in vivo is mediated primarily by the formation of an FN bridge formed between FAP-P of M. avium subsp. paratuberculosis and integrins on M cells.

Distinct fucosylation of M cells and epithelial cells by Fut1 and Fut2, respectively, in response to intestinal environmental stress

2011 ◽  
Vol 404 (3) ◽  
pp. 822-828 ◽  
Author(s):  
Kazutaka Terahara ◽  
Tomonori Nochi ◽  
Masato Yoshida ◽  
Yuko Takahashi ◽  
Yoshiyuki Goto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Environmental Stress ◽  
M Cells

Accessibility of glycolipid and oligosaccharide epitopes on rabbit villus and follicle-associated epithelium

2000 ◽  
Vol 278 (6) ◽  
pp. G915-G923 ◽  
Author(s):  
Nicholas J. Mantis ◽  
Andreas Frey ◽  
Marian R. Neutra
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Initial Step ◽  
Cell Types ◽  
Specific Cell ◽  
M Cells ◽  
Intestinal Epithelial ◽  
B Subunit ◽  
Maackia Amurensis ◽  
Maackia Amurensis Lectin

The initial step in many mucosal infections is pathogen attachment to glycoconjugates on the apical surfaces of intestinal epithelial cells. We examined the ability of virus-sized (120-nm) and bacterium-sized (1-μm) particles to adhere to specific glycolipids and protein-linked oligosaccharides on the apical surfaces of rabbit Peyer's patch villus enterocytes, follicle-associated enterocytes, and M cells. Particles coated with the B subunit of cholera toxin, which binds the ubiquitous glycolipid GM1, were unable to adhere to enterocytes or M cells. This confirms that both the filamentous brush border glycocalyx on enterocytes and the thin glycoprotein coat on M cells can function as size-selective barriers. Oligosaccharides containing terminal β(1,4)-linked galactose were accessible to soluble lectin Ricinus communistype I on all epithelial cells but were not accessible to lectin immobilized on beads. Oligosaccharides containing α(2,3)-linked sialic acid were recognized on all epithelial cells by soluble Maackia amurensis lectin II (Mal II). Mal II coated 120-nm (but not 1-μm) particles adhered to follicle-associated enterocytes and M cells but not to villus enterocytes. The differences in receptor availability observed may explain in part the selective attachment of viruses and bacteria to specific cell types in the intestinal mucosa.

scholarly journals Salmonella Transforms Follicle-Associated Epithelial Cells into M Cells to Promote Intestinal Invasion

2012 ◽  
Vol 12 (5) ◽  
pp. 645-656 ◽  
Author(s):  
Amin Tahoun ◽  
Simmi Mahajan ◽  
Edith Paxton ◽  
Georg Malterer ◽  
David S. Donaldson ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
M Cells

scholarly journals A novel M cell–specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses

2007 ◽  
Vol 204 (12) ◽  
pp. 2789-2796 ◽  
Author(s):  
Tomonori Nochi ◽  
Yoshikazu Yuki ◽  
Akiko Matsumura ◽  
Mio Mejima ◽  
Kazutaka Terahara ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Oral Vaccine ◽  
Goblet Cells ◽  
Carbohydrate Moiety ◽  
Mucosal Vaccine ◽  
M Cells ◽  
M Cell ◽  
Lethal Challenge ◽  
New Strategy ◽  
High Level

Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We established a novel M cell–specific monoclonal antibody (mAb NKM 16–2-4) as a carrier for M cell–targeted mucosal vaccine. mAb NKM 16–2-4 also reacted with the recently discovered villous M cells, but not with epithelial cells or goblet cells. Oral administration of tetanus toxoid (TT)– or botulinum toxoid (BT)–conjugated NKM 16–2-4, together with the mucosal adjuvant cholera toxin, induced high-level, antigen-specific serum immunoglobulin (Ig) G and mucosal IgA responses. In addition, an oral vaccine formulation of BT-conjugated NKM 16–2-4 induced protective immunity against lethal challenge with botulinum toxin. An epitope analysis of NKM 16–2-4 revealed specificity to an α(1,2)-fucose–containing carbohydrate moiety, and reactivity was enhanced under sialic acid–lacking conditions. This suggests that NKM 16–2-4 distinguishes α(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the α(1,2) fucose moiety and from non-α(1,2)-fucosylated epithelial cells. The use of NKM 16–2-4 to target vaccine antigens to the M cell–specific carbohydrate moiety is a new strategy for developing highly effective mucosal vaccines.

scholarly journals M CELLS ARE THE IMPORTANT POST IN THE INITIATION OF IMMUNE RESPONSE IN INTESTINE

2018 ◽  
Vol 8 (3) ◽  
pp. 263-272
Author(s):  
A. S. Bykov ◽  
A. V. Karaulov ◽  
D. A. Tsomartova ◽  
N. L. Kartashkina ◽  
V. L. Goriachkina ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Targeted Delivery ◽  
Oral Vaccine ◽  
Critical Event ◽  
M Cells ◽  
M Cell ◽  
Antigen Uptake ◽  
And Function

Microfold cells (M cells) are specialized intestinal epithelial cells that initiate mucosal immune responses. These unique phagocytic epithelial cells are specialized for the transfer of a broad range of particulate antigens and microorganisms across the follicle-associated epithelium (FAE) into the gut-associated lymphoid tissue (GALT) by a process termed transcytosis. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. Active sampling of intestinal antigen initiates regulated immune responses that ensure intestinal homeostasis. The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Several specialized mechanisms transport luminal antigen across the gut epithelium. Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells. Recent studies demonstrated that M cells utilize several receptors to recognize and transport specific luminal antigens. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity. How this process is regulated is largely unknown. This review aims to show a new understanding of the factors that influence the development and function of M cells; to show the molecules expressed on M cells which appear to be used as immunosurveillance receptors to sample pathogenic microorganisms in the gut; to note how certain pathogens appear to exploit M cells to inject the host; and, finally, how this knowledge is used to specifically "target" antigens to M cells to attempt to improve the efficacy of mucosal vaccines. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells.

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