[ODP-178] Intimate adhesion of Citrobacter rodentium is the cue to initiate anti-pathogen immune responses
Citrobacter rodentium is a murine pathogen that adheres to colonic epithelial cells and alters multiple cellular processes. Translocated intimin receptor (Tir) functions as receptor for Intimin, a bacterial adhesin, thereby mediating bacterial adhesion to epithelial cells. To determine the roles of intimate adhesion in the induction of specific immune responses upon C. rodentium infection, microbiota-depleted mice were infected with the Tir-F strain expressing full-length Tir or mutant strains expressing the C-terminal truncated Tir that is defective in Intimin binding and host cell actin polymerization. There were no differences in the colonization kinetics and antibodies responses against C. rodentium LPS among the strains, whereas antibodies against the virulence factors were only produced on Tir-F infection. Although there were no differences in the virulence factors mRNA expression, colonic hyperplasia, and bacterial translocation to the systemic organs irrespective of the strain, adhesion to colonic epithelial cells was reduced in the mutant strain-infected mice. Further, transcriptomic analysis indicated that robust inflammatory and immune responses were only induced in the Tir-F-infected mice. These findings suggest that Tir-mediated intimate adhesion induces inflammatory and immune responses, resulting in the induction of virulence factor-specific antibodies.