Identification of Adhesin–Receptor Interactions Driving Bacterial Translocation through M Cells

Abstract

Evaluation of: Hase K, Kawano K, Nochi T et al.: Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response. Nature 462, 226–230 (2009). M cells are specialized epithelial cells that transport antigens into lymphoid follicles. The mechanisms by which molecules, particles and microorganisms are transported by M cells remains poorly understood. Here, Hase and colleagues move a significant step forward by performing an extensive functional characterization of the GP2 interaction with FimH adhesin of bacterial type 1 pili. They show that GP2 is selectively expressed in M cells and functions as an endocytic receptor for type I-piliated bacteria. Comparison of Salmonella infection of wild-type and GP2-deficient mice confirmed the relevance of the GP2–FimH interaction in triggering an antigen-specific immune response in mice. Although this work supports the idea that the GP2-dependent pathway might constitute a new target for oral vaccine delivery it is necessary to be cautious as the reported enhancement of immune responses associated with GP2 and FimH expression were relatively modest. Since variation in FimH has been reported to have a major impact on glycoprotein binding, it might be possible to improve the efficacy of a putative vaccine using recombinant bacteria expressing high-affinity FimH variants. Alternative adhesin/receptor interactions are also likely to play a role in bacterial sampling by M cells and might also be exploited to enhance vaccine delivery.