The induction of mucosal immunity requires efficient
antigen delivery and adjuvant systems. Probiotic bacterial strains are considered to be very promising tools to address both of these needs. In particular, Bacillus subtilis spores are currently under investigation as a long-lived,
protease-resistant adjuvant system for different
antigens. Furthermore, a non-recombinant approach has been developed based on the stable adsorption of
antigen on the spore surface. In the present study, we explored this strategy as a means of modulating the immune response to wheat
gliadin, the triggering agent of
celiac disease (CD), an enteropathy driven by inflammatory CD4(+) T cells.
Gliadin adsorption was tested on untreated or autoclaved wild-type (wt) and mutant (cotH or cotE) spores. We found that
gliadin was stably and maximally adsorbed by autoclaved wt spores. We then tested the immune properties of the spore-adsorbed
gliadin in HLA-DQ8-transgenic mice, which express one of the two HLA heterodimers associated with CD. In vitro, spore-adsorbed
gliadin was efficiently taken up by mouse dendritic cells (DCs). Interestingly,
gliadin-pulsed DCs efficiently stimulated splenic CD4(+) T cells from mice immunised with spore-adsorbed
gliadin. Nasal pre-dosing with spore-adsorbed
gliadin failed to down-regulate the ongoing cellular response in
gliadin-sensitised DQ8 mice. Notably, naïve mice inoculated intranasally with multiple doses of spore-adsorbed
gliadin developed an intestinal
antigen-specific CD4(+) T cell-mediated response. In conclusion, our data highlight the ability of spore-adsorbed
gliadin to elicit a T-cell response in the gut that could be exploitable for developing immune strategies in CD.