Immunization of mice with Lactobacillus casei expressing a beta-intimin fragment reduces intestinal colonization by Citrobacter rodentium

ABSTRACT

countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to theTIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of -intimin (L.casei-Intcv) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogenCitrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice with L. casei-Intcv induced anti-IntcvIgA in feces but no IgG in sera. Conversely, anti-Intcv IgG was induced in the sera of mice after sublingualimmunization with purified Intcv. All vaccines were able to decrease C. rodentium recovery from feces. However,this reduction was more evident and sustained over time in mice immunized with L. casei-Intcv by thesublingual route. These mice also displayed an increase in interleukin 6 (IL-6) and gamma interferon (IFN- )secretion by spleen cells 10 days after infection. Additionally, oral or sublingual immunization of C3H/HePasmice, which are highly susceptible to C. rodentium infection, with L. casei-Intcv induced anti-Intcv antibodiesand significantly increased survival after challenge. Immunohistological analysis of colon sections revealedthat C. rodentium was located in deep fractions of the tissue from C3H/HePas mice immunized with L. casei whereas superficial staining was observed in colon sections from mice immunized with L. casei-Intcv. The results indicate that vaccines composed of L. casei expressing intimin may represent a promising approach and that the C3H/HePas infection model with C. rodentium can be used to evaluate potential vaccines against EPEC.