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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer 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.
OriginalsprogUdefineret/Ukendt
TidsskriftJournal of Immunology
Vol/bind202
Udgave nummer1 sup
ISSN0022-1767
StatusUdgivet - 2019
Udgivet eksterntJa

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