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Te Tari Moromoroiti me te Ārai Mate


Posted by on 7 July 2020 | Comments

12:00noon Monday 13th July
Room 208, 2nd floor,
Microbiology building, 
720 Cumberland Street

Hamish Angus

University of Otago, Department of Microbiology & Immunology


‘Crohn’s disease an in vitro analysis of T lymphocyte function and response to commensal microbes’


Crohn’s disease (CD) is a chronic, relapsing inflammation-induced pathology of the gastrointestinal tract.  The mechanisms underlying CD pathology, within individual patients, are difficult to understand due to the lack of readily available biologically relevantmodels.


Peripheral blood mononuclear cells (PBMCs) were compared between a cohort of patients with active CD and disease-free controls. CD patient PBMCs, produced higher amounts of IL-6, IL-17A, and TNF, and had a greater capacity for proliferation, compared to non-IBD controls. CD patient PBMC responses to the commensal bacteria, Faecalibacterium prausnitzii and Bacteroides fragilis, were distinct from non-IBD donors, suggesting altered immune response to commensal microbes.


A 2D intestinal organoid monolayer model was generated to examine epithelial responses to commensal bacteria, with or without an active immune presence. CD patient monolayers, but not those from non-IBD controls, had a reduction in monolayer integrity in the presence of F. prausnitzii, an effect exacerbated by immune cell presence.


Together, these data suggest CD patient epithelial cells have interactions with commensal species, leading to a breakdown in intestinal epithelial barrier function, which could result in bacterial translocation into the lumen and subsequent inflammation.