Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts

Hyungjun Yang, Hengameh Chloé Mirsepasi-Lauridsen, Carsten Struve, Joannie M Allaire, Else Bosman, Adeline Sivignon, Wayne Vogl, Caixia Ma, Gregor Reid, Xiaoxia Li, Andreas Munk Petersen, Kevan Jacobson, Sébastien Gouin, Nicolas Barnich, Hongbing Yu, Karen Angeliki Krogfelt, Bruce Andrew Vallance

Research output: Contribution to journalJournal articlepeer-review

Abstract

Ulcerative colitis (UC) is chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of E. coli strains related to extra-intestinal E. coli. These “pathobionts” exhibit pathogenic properties, but their potential to promote UC is unclear due to the lack of suitable animal models. Here, we established a mouse model using a representative UC pathobiont strain (p19A), and mice lacking single immunoglobulin and toll-interleukin 1 receptor domain (SIGIRR), a deficiency increasing susceptibility to gut infections. p19A was found to adhere to the cecal mucosa of Sigirr−/− mice, causing modest inflammation. Moreover, it dramatically worsened DSS induced colitis, in concert with adherence to, and penetration of the inflamed mucosa. This pathogenicity was lost in a p19A strain lacking the adhesin FimH; following treatment with FimH antagonists, or was attenuated when using a p19A strain lacking a-hemolysin genes. Thus UC pathobionts can worsen the course of colitis in susceptible hosts.
Original languageUndefined/Unknown
JournalJournal of Immunology
Volume202
Issue number1 sup
ISSN0022-1767
Publication statusPublished - 2019
Externally publishedYes

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