Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity

Abstract

Membranous (M) cells are specialized epithelial antigen-transporting cells scattered in the follicle-associated epithelium covering the gut lymphoid follicles such as Peyer's patches. Although the importance of M cells as a main portal for luminal antigens has long been recognized, molecular mechanisms for M-cell antigen uptake has remained largely elusive. We have recently found that glycoprotein 2 (GP2) is exclusively expressed on M cells among intestinal epithelial cells and serves as an uptake receptor for a subset of commensal and pathogenic bacteria. GP2 interacts with FimH, a major component of the type 1 pilus on the outer membrane of a subset of gram-negative enterobacilli such as E. coli and Salmonella enterica. Furthermore, GP2-FimH interaction is necessary for efficient uptake of FimH(+) bacteria by M cells and subsequent bacteria-specific mucosal immune responses. Pancreatic GP2 may also be involved in innate immunity by 'opsonization' of FimH(+) bacteria to facilitate their egestion in feces as well as translocation across the intestinal epithelium.

Keywords: Escherichia coli; FimH; IgA; M cells; Salmonella typhimurium; antigen uptake; bacteria; mucosal immunity; type I pili.

Figure 1

Confocal laser microscopy image of whole-mount staining of mouse Peyer's patch FAE. GP2 (green, left) and UEA-1 (red, middle) largely colocalize (merge, right). Note that GP2 staining is restricted to the FAE (an oval area in the middle of the field), while UEA-1 is not specific to FAE but also reacts strongly to mucin-secreting goblet cells in the villi. F-actin staining (blue) depicts the shape of villi surrounding PP. Scale bars, 100 µm.

Figure 2

Schematic domain structure of GP2 and THP. Domain structure of mouse GP2 and THP is drawn based on the information obtained through UniProt (http://www.uniprot.org/). FimH-binding region of GP2 is predicted based on our unpublished observation that a recombinant GP2 protein lacking the ZP domain still bound to E. coli in our in vitro binding assay.