Transcytosis of Bacterial Toxins across Mucosal Barriers

This chapter focuses on the biology and mechanisms of transcytosis for dIgA and IgG, and explains in detail the mechanism of transcytosis for cholera toxin. Reference is made to Shiga and Shiga-like enterotoxins that move across epithelial barriers by opportunistically exploiting similar mechanisms of vesicular transport Fcγ receptor (FcRn) is expressed in the polarized epithelial cells lining the intestine of adult humans. Cholera toxin (CT) binds a ganglioside receptor on the apical cell surface, enters the intestinal cell by non-clathrin-mediated endocytosis, and then moves retrograde into Golgi cisternae and endoplasmic reticulum (ER) to enter the cytoplasm and induce disease. To induce disease, CT must move from the cell surface into the endosome and then retrograde into the ER. To distinguish the transcytotic pathway that involves transit through the Golgi apparatus from that defined by transcytosis of the pIgR and the FcRn, the authors have termed the process of CT trafficking across epithelial cells as indirect transcytosis. It is well documented that CT and LTI represent the most potent mucosal immunogens and adjuvants recognized to date. Such efficiency in eliciting inductive immunity after application to mucosal surfaces, not seen with other ingested proteins of comparable size, implies that CT exhibits an ability to encounter and perhaps act on antigen-presenting cells of the mucosal immune system. Transcytosis of both dIgA and IgG depends on sorting motifs embedded within the protein structures of the pIgR and the FcRn.