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P666. Type 1 pili and long polar fimbriae are essential for induction of host–microbiota mutualism by adherent-invasive Escherichia coli, even in the presence of competing intestinal microbes

E. Vazeille1, M.L. Balmer2, B. Chassaing1, S. Stefan Müller2, T. Thomas Schaffer2, E. Slack3, S. Pfister4, M.B. Geuking5, D. Lottaz2, A.J. Macpherson2, S. Hapfelmeier3, K.D. McCoy2, A. Darfeuille-Michaud1, E. Vazeille1, 1M2iSH UMR 1071 Inserm/Université d'Auvergne USC INRA 2018, Centre Biomédical de Recherche et Valorisation, Clermont-Ferrand, France, 2University Bern, Maurice E Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin, Inselspital, Bern, Switzerland, 3Institute of Microbiology, D-BIOL, ETH Zürich, Zürich, Switzerland, 4University Bern, Institute for Infectious Diseases, Bern, Switzerland, 5University of Bern, Department Klinische Forschung, Bern, Switzerland

Background

The ileal involvement of Crohn's disease (CD) is associated with an increase in pathogenic adherent-invasive E. coli (AIEC) and several serological markers specific for microbial antigens have been identified in subgroups of patients with CD. The aim of the present study was to compare the adaptive immune responses to intestinal colonization by AIEC in presence or absence of a commensal microbiota, and to define the role of known AIEC virulence factors.

Methods

Germ-free or Altered Schaedler Flora animals were orally infected with non-pathogenic E. coli K-12, AIEC LF82 and LF82 mutants unable to produce type 1 pili and long polar fimbriae. Bacterial gastrointestinal colonization and immunoglobulin responses were assessed in both mice models.

Results

Experiments in mice showed a preference (complete for germ-free mice and partial for ASF mice) of AIEC bacteria to colonize ileal mucosa of mice regardless of the presence of a limited commensal flora. Specific serum IgM, IgG1 and IgG2b responses, which are known to enhance systemic bacterial clearance, were only observed against AIEC bacteria and not against non-pathogenic E. coli K-12. Among the known AIEC virulence factors, type 1 pili and long polar fimbriae were important for ileum tropism, tissue invasion and induction of systemic AIEC-specific IgM and IgG antibody responses. However, efficient systemic immune response was observed in their absence suggesting that other and yet unidentified virulence factors mediating intestinal translocation and serum reactivity exist.

Conclusion

We observed a high immunogenicity of type 1 pili and Long Polar Fimbriae, highly expressed under gastrointestinal growth conditions. This study indicated also that bacterial virulence factors act in concert to elicit their pathogenic potential whereas the host-immune system evolved strong mechanisms to detect and target bacteria regardless of their bacterial surface arming.