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

Gut Pathogens

Nicole Tegtmeyer¹  Manja Boehm¹  Steffen Backert¹  Anna-Maria Schmidt²  Markus M. Heimesaat²  Ulrike Escher²  Soraya Mousavi²  Stefan Bereswill² 

[1] 0000 0001 2107 3311, grid.5330.5, Institute for Microbiology, Department of Biology, Friedrich Alexander University Erlangen/Nuremberg, Erlangen, Germany;Department of Microbiology, Institute of Microbiology, Infectious Diseases and Immunology, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195, Berlin, Germany;

关键词: Campylobacter jejuni;    FlaA/B;    CadF;    Flagellin;    IL-10 mice;    Secondary abiotic (gnotobiotic) mice;    Pro-inflammatory immune responses;    Host–pathogen-interaction;    Bacterial translocation;    Intestinal immunopathology;    Extra-intestinal immune responses;    Systemic immune responses;   

DOI  :  10.1186/s13099-019-0306-9

来源: publisher

【 摘 要 】

BackgroundCampylobacter jejuni 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 C. jejuni 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 C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF (Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively.Methods and resultsTherefore, abiotic IL-10−/− mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (ΔflaA/B) or cadF (ΔcadF) deletion mutants. Cultural analyses revealed that WT and ΔcadF but not ΔflaA/B 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 ΔflaA/B strain did not result in overt campylobacteriosis, whereas mice infected with ΔcadF 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 C. jejuni ΔcadF or WT, but not ΔflaA/B strain infection.ConclusionFor the first time, our observations revealed that the C. jejuni 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 C. jejuni virulence factors in induction and progression of disease.

【 授权许可】

CC BY