Regional differences in glycoconjugates of intestinal M cells in mice: potential targets for mucosal vaccines

Giannasca, Paul J.; Giannasca, K T; Falk, Per; Gordon, JoyceM.; Neutra, Marian R.

doi:10.1152/ajpgi.1994.267.6.g1108

Cited by 101 publications

(114 citation statements)

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“…M-cells and enterocytes formed an irregular mosaic-like pattern that was detected by confocal laser scanning microscopy, not only on the dome epithelium but also in the upper third of the dome-associated crypts. In contrast to the situation described for Epon sections of murine Peyer's patches (Giannasca et al 1994), the lectinlabeled cells were oriented to all sides of these crypts (see lower left corner of Figure 2). According to the generally accepted theory of crypt cell origin, differentiation, and renewal (Cheng and Leblond 1974), the different types of gut epithelial cells develop from undifferentiated crypt stem cells.…”

Section: Discussioncontrasting

confidence: 71%

“…Although some of the confocal images gave the impression that three subtypes of M-cells could exist according to the expression of ␣ 1-2-linked fucose or GalNAc, at the electron microscopic level no distinct subtypes were found, but rather a continuous spectrum of labeling intensities. Heterogeneity among the M-cells of individual domes has likewise been reported for the binding of the lectins UEA-I, AAA, and EEA to M-cells of murine Peyer's and cecal patches (Giannasca et al 1994;Clark et al 1995) and for the binding of UEA-I and Lotus lectin to M-cells in the palatine tonsil of rabbits (Gebert 1996). The lectin labeling of living tissue performed in the present study demonstrates that variations in the saccharide composition of the apical membrane of M-cells indeed exist in the living system, which probably play a role in the differential adherence to and uptake of antigens by M-cells.…”

Section: Discussionmentioning

confidence: 69%

“…Although the biological significance of these membrane-bound glycoconjugates is not completely understood (Clark et al 1993;Gebert and Hach 1993;Jepson et al 1993a;Giannasca et al 1994), the rabbit cecal patch represents an appropriate model for studying the origin, differentiation, and migration of M-cells.…”

Section: Discussionmentioning

confidence: 99%

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Glycoconjugate Expression Defines the Origin and Differentiation Pathway of Intestinal M-cells

Gebert

Posselt

1997

J Histochem Cytochem.

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SUMMARYIntestinal M-cells are specialized epithelial cells located in the domes of the gut-associated lymphoid tissues, which transport antigens from the lumen to the underlying lymphoid tissue, thereby initiating immune reactions. It is assumed that M-cells arise from stem cells in the crypts, from which they migrate to the top of the domes. To study the differentiation pathway of M-cells, we used the rabbit cecal lymphoid patch in which the M-cells express high levels of ␣ 1-2-linked fucose and N -acetyl-galactosamine residues in their apical membrane. Dome areas were labeled with fluorescein-and rhodamine-conjugated lectins specific for ␣ 1-2-linked fucose and N -acetyl-galactosamine in vivo and in vitro, and were observed with confocal laser scanning microscopy. Ultrathin sections were double labeled with lectin-gold conjugates and the labeling density was quantified by computer-based image analysis. All cecal patch M-cells expressed ␣ 1-2-linked fucose and N -acetyl-galactosamine, but the amount of the two saccharides varied considerably depending on the position of the M-cells at the base, flank, or top of the dome. In eight of 18 rabbits studied, radial strips of M-cells with common glycosylation patterns were observed, each strip associated with an individual crypt. Confocal microscopy revealed that lectinlabeled M-cells were not restricted to the dome epithelium but were also detected in the upper third of crypts surrounding the domes. The results show that M-cells are heterogeneous concerning the glycosylation pattern of membrane glycoconjugates. This pattern is modified as the M-cells differentiate and migrate from the base to the top of the dome. Radial strips of M-cells with a common proclivity of glycoconjugate expression suggest that those M-cells that derive from the same crypt have a clonal origin. The presence of (pre-) M-cells in the crypts surrounding the domes indicates that M-cells derive directly from undifferentiated crypt cells and do not develop from differentiated enterocytes.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 69%

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Glycoconjugate Expression Defines the Origin and Differentiation Pathway of Intestinal M-cells

Gebert

Posselt

1997

J Histochem Cytochem.

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“…GP2 is a heavily glycosylated protein that is an established marker for M cells (47). Before the use of the GP2 antibody, this protein was identified on M cells with UEA-1, a lectin with specificity for the α1-2-linked fucose structures found in the blood group antigens on this glycoprotein (33,(47)(48)(49). The interaction of S. flexneri polysaccharide with GP2 provides further evidence for a polysaccharide-dependent adherence mechanism for S. flexneri that is likely to involve binding to host glycoconjugates identified in our array screen and confirmed with SPR.…”

Section: Discussionmentioning

confidence: 99%

Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells

Day

Tran

Semchenko

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

107

104

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Cells from all domains of life express glycan structures attached to lipids and proteins on their surface, called glycoconjugates. Cell-tocell contact mediated by glycan:glycan interactions have been considered to be low-affinity interactions that precede highaffinity protein-glycan or protein-protein interactions. In several pathogenic bacteria, truncation of surface glycans, lipooligosaccharide (LOS), or lipopolysaccharide (LPS) have been reported to significantly reduce bacterial adherence to host cells. Here, we show that the saccharide component of LOS/LPS have direct, high-affinity interactions with host glycans. Glycan microarrays reveal that LOS/LPS of four distinct bacterial pathogens bind to numerous host glycan structures. Surface plasmon resonance was used to determine the affinity of these interactions and revealed 66 high-affinity host-glycan:bacterial-glycan pairs with equilibrium dissociation constants (K D ) ranging between 100 nM and 50 μM. These glycan:glycan affinity values are similar to those reported for lectins or antibodies with glycans. Cell assays demonstrated that glycan:glycan interaction-mediated bacterial adherence could be competitively inhibited by either host cell or bacterial glycans. This is the first report to our knowledge of high affinity glycan:glycan interactions between bacterial pathogens and the host. The discovery of large numbers of glycan:glycan interactions between a diverse range of structures suggests that these interactions may be important in all biological systems.H ost surface glycosylation is ubiquitous and is targeted by pathogenic bacteria, viruses, fungi and parasites for adherence and toxin binding and by glycosidases (1). Escherichia coli type 1 fimbriae, FimH, is one of the most widely studied glycanrecognizing protein adhesins, with specificity for monomannose to oligomannose structures with the variability of the mannose structure bound leading to different tissue tropism (2). Other glycan-recognizing adhesins expressed by bacteria include the following: Pseudomonas aeruginosa lectins 1 and 2 (PA-IL and PA-IIL) that have specificity for galactose and fucose, respectively (3); Helicobacter pylori SabA, specific for sialic acid containing glycoconjugates including sialyLewis X; and BabAspecific for fucosylated glycoconjugates including Lewis B (4, 5). Although there are numerous known glycan binding adhesins, the adhesins of some bacteria that interact with host surface glycans remain unknown.Direct interactions between surface glycans (glycan:glycan interactions) have been reported in sea sponges as heterogenous glycan interactions, and in mouse embryo development and cancer where homodimers of Lewis X (LeX) or ganglioside structures play a role in cell adhesion and growth factor receptor interactions (6, 7). Outside of these reports, glycan:glycan interactions, when noted, have generally been considered to be low-affinity, weak interactions (8) that precede high-affinity protein:glycan or protein:protein interactions (1, 2, 5, 9).Interestingly, there...

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“…UEA-1 and Aleuria aurantia lectin have high specificity for the carbohydrate moiety ␣-L-fucose located on the apical membranes of mouse M cells (19,21,52). There have been successful efforts made in in vivo targeting in mouse M cells by conjugating UEA-1 to polymerized liposomes (33) and latex particles (53), or by coating poly(D, L-lactide-coglycolide) particles with the A. aurantia lectin (52).…”

Section: Discussionmentioning

confidence: 99%

Targeted Delivery of Immunogen to Primate M Cells with Tetragalloyl Lysine Dendrimer

Misumi

Masuyama

Takamune

et al. 2009

The Journal of Immunology

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Effective uptake of Ags by specialized M cells of gut-associated lymphoid tissues is an important step in inducing efficient immune responses after oral vaccination. Although stable nontoxic small molecule mimetics of lectins, such as synthetic multivalent polygalloyl derivatives, may have potential in murine M cell targeting, it remains unclear whether synthetic multivalent polygalloyl derivatives effectively target nonhuman and human M cells. In this study, we evaluated the ability of a tetragalloyl derivative, the tetragalloyl-d-lysine dendrimer (TGDK), to target M cells in both in vivo nonhuman primate and in vitro human M-like cell culture models. TGDK was efficiently transported from the lumen of the intestinal tract into rhesus Peyer’s patches by M cells and then accumulated in germinal centers. Oral administration of rhesus CCR5-derived cyclopeptide conjugated with TGDK in rhesus macaque resulted in a statistically significant increase in stool IgA response against rhesus CCR5-derived cyclopeptide and induced a neutralizing activity against SIV infection. Furthermore, TGDK was specifically bound to human M-like cells and efficiently transcytosed from the apical side to the basolateral side in the M-like cell model. Thus, the TGDK-mediated vaccine delivery system represents a potential approach for enabling M cell-targeted mucosal vaccines in primates.

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Regional differences in glycoconjugates of intestinal M cells in mice: potential targets for mucosal vaccines

Cited by 101 publications

References 0 publications

Glycoconjugate Expression Defines the Origin and Differentiation Pathway of Intestinal M-cells

Glycoconjugate Expression Defines the Origin and Differentiation Pathway of Intestinal M-cells

Glycan:glycan interactions: High affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells

Targeted Delivery of Immunogen to Primate M Cells with Tetragalloyl Lysine Dendrimer

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