1887

Chapter 12 : Transcytosis of Bacterial Toxins across Mucosal Barriers

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Transcytosis of Bacterial Toxins across Mucosal Barriers, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817893/9781555812454_Chap12-1.gif /docserver/preview/fulltext/10.1128/9781555817893/9781555812454_Chap12-2.gif

Abstract:

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.

Citation: Dickinson B, Lencer W. 2003. Transcytosis of Bacterial Toxins across Mucosal Barriers, p 173-186. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch12

Key Concept Ranking

Bacterial Proteins
0.6574881
Bacterial Toxins
0.5032729
0.6574881
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Absorptive mechanisms of transporting epithelia. (A) Polarized epithelial cells lining mucosal surfaces form a barrier that prevents penetration of macromolecules and bacterial toxins beyond the epithelium. (B) Some molecules move between cells and pass through the tight junctions by the process of paracellular transport. (C) In contrast, small solutes such as sodium and glucose cross the epithelial barrier by the action of specific transporters and channels that facilitate their movement in a process termed transcellular transport.

Citation: Dickinson B, Lencer W. 2003. Transcytosis of Bacterial Toxins across Mucosal Barriers, p 173-186. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Absorptive mechanisms of transporting epithelia. Direct transcytosis of dIgA-pIgR complexes (left) is initiated by binding of dIgA to the pIgR at the basolateral surface of the epithelial cell, which stimulates endocytosis of the complex into an early endosome (EE). Here, the dIgA-pIgR complex moves away from fluid-phase cargo and other membrane components targeted to the late endosome or lysosome for degradation. The dIgA-pIgR complex then traffics into the common endosome (CE) and then again to the apical recycling endosome (ARE). Transport from the common endosome into the apical recycling endosome is a hallmark of polarized sorting of the pIgR in the transcytotic pathway. In indirect transcytosis (right panel), CT enters the polarized epithelial cell by binding GM1 at the apical membrane and then moves via an early endosomal compartment (AE) into the Golgi complex. In the Golgi, the C-terminal KDEL motif on the A-subunit facilitates retrograde movement of the CT-GM1 complex through the Golgi stack and into the ER. In the ER, the A-subunit separates from the B-subunit-GM1 complex, unfolds, and translocates across from the ER into the cytosol in a process catalyzed by the ER lumenal chaperone protein disulfide isomerase (PDI). Alternatively, the A-subunit may remain attached to the B-subunit after translocation and moves to the basolateral membrane by entering the anterograde transport vesicles (BE) and moving back out the secretory pathway.

Citation: Dickinson B, Lencer W. 2003. Transcytosis of Bacterial Toxins across Mucosal Barriers, p 173-186. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Immunolocalization of FcRn in polarized T84 monolayers and normal adult human small intestinal mucosa. (a) Whole-mount T84 monolayers visualized en face show a diffuse, punctate staining pattern. The Z0-1 image was captured slightly above the focal plane of FcRn. (b) FcRn staining of whole-mount T84 monolayers visualized as confocal vertical sections. (c) FcRn staining was absent in the presence of an isotype-matched, irrelevant antiserum. (d and e) FcRn staining was absent in the presence of an irrelevant antiserum or with secondary antibody alone. (f) Villous enterocytes of normal adult human small intestine show delicate linear staining in the region of the apical cytoplasmic membrane. (g) Crypt enterocytes show an apical and punctuate staining pattern visible not only at the level of the apical cytoplasmic membrane, but also in the apical cytoplasm below the level of the apical membrane. (See Color Plates following p. 256.)

Citation: Dickinson B, Lencer W. 2003. Transcytosis of Bacterial Toxins across Mucosal Barriers, p 173-186. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Crystal structure of CT. A ribbon diagram based on the crystal structure of the CT holotoxin is shown viewed from the side. Each subunit is labeled. This figure was kindly provided by Ethan Merritt and Wim Hol, University of Washington, Seattle.

Citation: Dickinson B, Lencer W. 2003. Transcytosis of Bacterial Toxins across Mucosal Barriers, p 173-186. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Transcytosis of CT B-subunit across polarized T84 cell monolayers and effect of mutation in KDEL on CT trafficking through the transcytotic pathway. Transcytosis of KDEL-mutant (m) and wild-type (wt) CT from apical to basolateral membranes was assessed by selective cell surface biotinylation. T84 cell monolayers grown on permeable supports were exposed continuously to 1 nM of KDEL-mutant or wt CT at the apical cell surface at the indicated temperatures and times followed by cell surface biotinylation at either the apical (lane 1) or basolateral (lanes 2–10) surface. The upper panel shows a Western blot to demonstrate that each lane contains equivalent amounts of immunoprecipitated CT B subunit. The lower panel shows the avidinhorseradish peroxidase (HRP) blot of the same experiment, revealing biotinylated toxin. The first lane shows that CT B subunit can be labeled with biotin while bound to GM1 at the apical plasma membrane (positive control). At 4°C, a temperature that completely inhibits vesicular traffic, CT B does not reach the basolateral membrane, as indicated by the absence of biotinylated CT B subunit (lane 2). Lanes 7 and 8 show that in cells incubated at 27°C for 160 min, basolaterally applied biotin has now labeled a fraction of the Bsubunit at the basolateral membrane, indicating that both the KDEL-mutant and wt CT reach the basolateral membrane by transcytosis. The amount of the KDEL-mutant CT reaching the basolateral membrane is approximately fivefold less than that of wt CT, indicating that transcytosis for the KDELmutant CT proceeds more slowly than for wt toxin. From reference 6 with permission.

Citation: Dickinson B, Lencer W. 2003. Transcytosis of Bacterial Toxins across Mucosal Barriers, p 173-186. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817893.chap12
1. Abrahamson, D. R.,, A. Powers,, and R. Rodewald. 1979. Intestinal absorption of immune complexes by neonatal rats: a route of antigen transfer from mother to young. Science 206:567569.
2. Acheson, D. W.,, R. Moore,, S. De Breucker,, L. Lincicome,, M. Jacewicz,, E. Skutelsky,, and G. T. Keusch. 1996. Translocation of Shiga toxin across polarized intestinal cells in tissue culture. Infect. Immun. 64:32943300.
3. Brown, P. S.,, E. Wang,, B. Aroeti,, S. J. Chapin,, K. E. Mostov,, and K. W. Dunn. 2000. Definition of distinct compartments in polarized Madin-Darby canine kidney (MDCK) cells for membrane-volume sorting, polarized sorting and apical recycling. Traffic 1:124140.
4. Dickinson, B. L.,, K. Badizadegan,, Z. Wu,, J. C. Ahouse,, X. Zhu,, N. E. Simister,, R. S. Blumberg,, and W. I. Lencer. 1999. Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J. Clin. Invest. 104:903911.
5. Lencer, W. I. 2001. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin. Am. J. Physiol. Gastrointest. Liver Physiol. 280:G781786.
6. Lencer, W. I.,, C. Constable,, S. Moe,, M. Jobling,, H. M. Webb,, S. Ruston,, J. L. Madara,, T. Hirst,, and R. Holmes. 1995. Targeting of cholera toxin and E. coli heat labile toxin in polarized epithelia: role of C-terminal KDEL. J. Cell Biol. 131:951962.
7. Lencer, W. I.,, S. Moe,, P. A. Rufo,, and J. L. Madara. 1995. Transcytosis of cholera toxin subunits across model human intestinal epithelia. Proc. Natl. Acad. Sci. USA 92: 1009410098.
8. Maksymowych, A. B.,, and L. L. Simpson. 1998. Binding and transcytosis of botulinum neurotoxin by polarized human colon carcinoma cells. J. Biol. Chem. 273:2195021957.
9. Merritt, E. A.,, S. Sarfaty,, F. van der Akker,, C. L’Hoir,, J. A. Martial,, and W. G. J. Hol. 1994. Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide. Protein Sci. 3:166175.
10. Mostov, K. E.,, M. Friedlander,, and G. Blobel. 1984. The receptor for transepithelial transport of IgA and IgM contains multiple immunoglobulin-like domains. Nature 308:3743.
11. Simister, N. E.,, and A. R. Rees. 1985. Isolation and characterization of an Fc receptor from neonatal rat small intestine. Eur. J. Immunol. 15:733738.
12. Tsai, B.,, C. Rodighiero,, W. I. Lencer,, and T. Rapoport. 2001. Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104:937948.
13. Wolf, A. A.,, M. G. Jobling,, S. Wimer-Mackin,, J. L. Madara,, R. K. Holmes,, and W. I. Lencer. 1998. Ganglioside structure dictates signal transduction by cholera toxin in polarized epithelia and association with caveolae-like membrane domains. J. Cell Biol. 141:917927.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error