Abstract

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.

Highlights

  • The molecular basis of antigen uptake by Microfold cells (M cells) has been gradually identified in the last decade

  • 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 and their toxins

  • Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells

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Summary

Introduction

Сообщалось, что повышенное количество М-клеток в эпителии кишечника после системной RANKL-терапии улучшает захват перорально вводимых антигенов из просвета кишечника и тем самым улучшает антигенспецифический иммунитет к слизистой оболочке [39]. Глубокое понимание молекулярных механизмов, которые лежат в основе RANKL-опосредованной индукции дифференцировки М-клеток в кишечнике, может привести к идентификации новых механизмов для усиления иммунитета слизистой оболочки или к разработке стратегий блокирования фекально-орального механизма передачи инфекций. При отсутствии M-клеток аккумуляция прионов в Пейеровой бляшке и последующая нейроинвазия были заблокированы, что свидетельствует о транслокации прионов через эпителий кишечника в ассоциации с M-клетками [11].

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