M cell-targeted mucosal vaccine strategies

Abstract

Immune responses in the aerodigestive tract are characterized by production and transport of specific IgA antibodies across the epithelium to act as a first line of defense against pathogens in the external environment. To sample antigens on mucosal surfaces in the intestine and upper respiratory tract, the immune system relies on a close collaboration between specialized antigen-sampling epithelial M cells and lymphoid cells. Depending on various factors, local antigen presentation in the mucosal tissue leads to tolerance or initiation of an active immune response. Recently, molecules that could be used to target vaccine antigens to apical M cell surfaces have been identified. Here we review the M cell-targeted vaccine strategy, an approach that could be used to enhance uptake and efficacy of vaccines delivered in the nasal cavity or intestine.

Fig. 1

Diagram of M cells in the follicle-associated epithelium. M cells have tight junctions and desmosomes in contact with adjacent columnar epithelial cells. Luminal surfaces of M cells are characterized by short microvilli, a thin mucus layer, small cytoplasmic vesicles, a reduced glycocalyx and sparse lysosomes. The basolateral surface of the M cells forms an intraepithelial pocket that contains DC, T cells or B cells

Fig. 2

MALT-dependent and -independent antigen-sampling system at aerodigestive surfaces. Antigens are captured by M cells located in follicle-associated epithelium (FAE) of lymphoid follicles, intestinal villi or the epithelial cell layer in the nasal cavity. The antigens are then transported to subepithelial DC for processing and presentation. Alternatively, lamina propia or intraepithelial DC extends their dendrites through the epithelial layer for direct capture of luminal antigens. Antigen uptake through M cells in FAE of MALT leads to the induction of mucosal IgA responses. On the other hand, M cells located in the intestinal villi or nasal epithelium as well as intraepithelial DC are thought to play a critical role in the induction of systemic IgG responses in addition to mucosal IgA

Fig. 3

FAE M cell-targeting antigen delivery system for induction of active or quiescent immunity. Different fusion molecules consisting of antigen and M cell-targeting molecules have been shown to effectively induce Th2 type cell-mediated protective immunity and/or T_reg cell-mediated mucosal tolerance