Yersiniabactin-Producing Adherent/Invasive Escherichia coli Promotes Inflammation-Associated Fibrosis in Gnotobiotic Il10 −/− Mice
| Autor: | Raad Z. Gharaibeh, Cory Brouwer, Lyndsey N. Moore, Florian Rieder, Ilyssa O. Gordon, Jeremy Herzog, Melissa Ellermann, Kenneth W. Simpson, Laura Fulbright, Allison R. Rogala, Christopher A. Broberg, Lacey R. Lopez, Aaron Rothemich, R. Balfour Sartor, Christian Jobin, Janelle C. Arthur, Belgin Dogan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Immunology Inflammation Biology Microbiology Yersiniabactin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fibrosis medicine Colitis Fibroblast Receptor medicine.disease Pathogenicity island 3. Good health Interleukin 10 030104 developmental biology Infectious Diseases medicine.anatomical_structure chemistry 030211 gastroenterology & hepatology Parasitology medicine.symptom |
| Zdroj: | Infection and Immunity. 87 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Fibrosis is a significant complication of intestinal disorders associated with microbial dysbiosis and pathobiont expansion, notably Crohn’s disease (CD). Mechanisms that favor fibrosis are not well understood, and therapeutic strategies are limited. Here we demonstrate that colitis-susceptible Il10-deficient mice develop inflammation-associated fibrosis when monoassociated with adherent/invasive Escherichia coli (AIEC) that harbors the yersiniabactin (Ybt) pathogenicity island. Inactivation of Ybt siderophore production in AIEC nearly abrogated fibrosis development in inflamed mice. In contrast, inactivation of Ybt import through its cognate receptor FyuA enhanced fibrosis severity. This corresponded with increased colonic expression of profibrogenic genes prior to the development of histological disease, therefore suggesting causality. fyuA-deficient AIEC also exhibited greater localization within subepithelial tissues and fibrotic lesions that was dependent on Ybt biosynthesis and corresponded with increased fibroblast activation in vitro. Together, these findings suggest that Ybt establishes a profibrotic environment in the host in the absence of binding to its cognate receptor and indicate a direct link between intestinal AIEC and the induction of inflammation-associated fibrosis. |
| Databáze: | OpenAIRE |
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