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

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Details zur Publikation

Autorinnen und Autoren: Schmidt AM, Escher U, Mousavi S, Tegtmeyer N, Böhm M, Backert S, Bereswill S, Heimesaat MM
Zeitschrift: Gut Pathogens
Jahr der Veröffentlichung: 2019
Band: 11
Heftnummer: 1
ISSN: 1757-4749


Abstract

Background: Campylobacter 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 results: Therefore, 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. Conclusion: For 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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Backert, Steffen Prof. Dr.
Lehrstuhl für Mikrobiologie
Böhm, Manja Dr.
Lehrstuhl für Mikrobiologie


Einrichtungen weiterer Autorinnen und Autoren

Charité - Universitätsmedizin Berlin


Zitierweisen

APA:
Schmidt, A.M., Escher, U., Mousavi, S., Tegtmeyer, N., Böhm, M., Backert, S.,... Heimesaat, M.M. (2019). Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model. Gut Pathogens, 11(1). https://dx.doi.org/10.1186/s13099-019-0306-9

MLA:
Schmidt, Anna Maria, et al. "Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model." Gut Pathogens 11.1 (2019).

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Zuletzt aktualisiert 2019-03-06 um 11:08