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Targeting to intestinal M cells
M A Jepson1, M A Clark, N Foster
1Department of Physiological Sciences, University of Newcastle upon Tyne Medical School, UK.
Abstract:
The specialised, antigen-transporting, epithelial M cells in the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute the primary target for oral delivery of vaccines. Our studies have shown that polystyrene microspheres selectively bind to, and are efficiently transcytosed by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch FAE is an order of magnitude lower than that of polystyrene microspheres. Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, supporting the potential of such microspheres as vehicles for oral vaccine delivery. Comparison of the binding of polystyrene microspheres by murine FAE revealed this to be markedly less extensive than by rabbit FAE. These data demonstrate that microsphere binding by M cells depends on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere delivery vehicles. One such approach is the incorporation of molecules with inherent binding specificity for M cells. Lectin-binding studies have revealed that M cells exhibit pronounced regional and species variation in glycoconjugate expression. In murine intestine, certain lectins bind selectively to M cells either in Peyer's patches or caecum, or at both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M cells in ligated segments of murine intestine have also been demonstrated. While several lectins display strong selectivity for rabbit caecal M cells, none to date have been identified with specificity for rabbit or rat Peyer's patch M cells. Knowledge of human M cells is limited and no lectin has yet been identified with specificity for these cells. However, at least one lectin exhibits binding specificity for FAE in the human ileum. In the future, knowledge of the regional patterns of M cell carbohydrate expression within a species may allow lectins to be utilised to target selectively antigenic material to the mucosal immune system at specific locations.
Insights
Microsphere binding to M cells for oral vaccine delivery varies by material and species. Surface modifications, like using lectins, can improve targeting to M cells for enhanced vaccine transport.
Area of Science:
- Immunology
- Biomaterials Science
- Gastroenterology
Background:
- M cells in the follicle-associated epithelium (FAE) are key targets for oral vaccine delivery.
- Understanding M cell interactions with delivery vehicles is crucial for effective mucosal immunization.
Purpose of the Study:
- To investigate the binding and transcytosis of different microspheres by M cells.
- To explore the potential of surface modifications, such as lectin conjugation, for targeted M cell delivery.
Main Methods:
- Studied polystyrene and poly(DL-lactide-co-glycolide) microsphere binding and transcytosis in rabbit and murine Peyer's patch M cells.
- Investigated lectin binding specificity to M cells in different species and regions of the intestine.
- Assessed the targeting and transcytosis of lectin-conjugated microspheres in murine intestinal segments.
Main Results:
- Polystyrene microspheres showed higher binding to rabbit M cells than biodegradable microspheres.
- Biodegradable microspheres, though not M cell-specific, were efficiently transcytosed by bound M cells.
- M cell binding varied significantly between species (rabbit vs. murine) and microsphere surface properties.
- Lectins demonstrated species- and site-specific binding to M cells, enabling targeted delivery in murine models.
Conclusions:
- Microsphere binding to M cells is influenced by surface characteristics and species-specific variations.
- Surface modification with lectins offers a promising strategy for enhancing targeted oral vaccine delivery via M cells.
- Further research into M cell glycoconjugate expression can optimize lectin-based targeting for mucosal immunization.