Immunopathological properties of the flagellins and the adhesin CadF as assessed in a clinical murine infection model.

Background: infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host-pathogen interactions is still limited. Our group has established a clinical infection model based on abiotic IL-10 mice mimicking key features of human campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important virulence factors FlaA and FlaB and the major adhesin CadF ( adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively.

Methods And Results: Therefore, abiotic IL-10 mice were perorally infected with strain 81-176 (WT) or with its isogenic (Δ) or (Δ) deletion mutants. Cultural analyses revealed that WT and Δ but not Δ bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the Δ strain did not result in overt campylobacteriosis, whereas mice infected with Δ or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following Δ or WT, but not Δ strain infection.

Conclusion: For the first time, our observations revealed that the flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine campylobacteriosis. Furthermore, the secondary abiotic IL-10 infection model has been proven suitable not only for detailed investigations of immunological aspects of campylobacteriosis, but also for differential analyses of the roles of distinct virulence factors in induction and progression of disease.