Microbiota-mediated fine-tuning of the threshold of intestinal inflammasome activation in host-microbial mutualism

Ronchi, Francesca; Rupp, Sandra; Steinert, Anna; Wyss, Madeleine; McCoy, Kathleen; Macpherson, Andrew (2014). Microbiota-mediated fine-tuning of the threshold of intestinal inflammasome activation in host-microbial mutualism (Unpublished). In: EMIG2014. Glasgow, UK.

The inflammasome is a complex of proteins that controls the activity of caspase-1, pro-IL-1b and pro-IL-18. It acts in inflammatory processes and in pyropoptosis. The lower intestine is densely populated by a community of commensal bacteria that, under healthy conditions, are beneficial to the host. Some evidence suggests that the gut microbiota influences regulation of the inflammasome. Components of inflammasomes have been shown to have a protective function against development of experimental colitis, dependent on IL-18 production. However the precise mechanisms and the role of the inflammasome in maintaining a healthy host-microbial mutualism remains unknown. To address this question, we have performed axenic (GF) and gnotobiotic in vivo experiments to investigate how the inflammasome components mainly at the level of intestinal epithelial cells (IECs) are regulated under different hygiene conditions. We have established that gene expression of the inflammasome components NLRC4, NLRP3, NLRP6, NLRP12, caspase-1, ASC and IL-18 do not differ between germ-free and colonised conditions under steady-state. In contrast, induction in IL-18 was observed following infection with the pathobiont Segmented Filamentous Bacteria or the pathogen C. rodentium. Additional preliminar findings suggest that a more diverse intestinal flora, like specific pathogen-free (SPF) flora, is more efficient in inducing basal activation of the inflammasome and especially production of IL-18 by IECs, shortly after colonisation. We are also in the process of testing if basal activation of the inflammasome upon intestinal colonization with commensal bacteria helps to protect the host from potential pathobiont bacteria, like C. rodentium, SFB, Prevotella and TM7.

Item Type:

Conference or Workshop Item (Speech)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Ronchi, Francesca; Rupp, Sandra; Steinert, Anna; Wyss, Madeleine; McCoy, Kathleen and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

04 May 2015 08:12

Last Modified:

04 May 2015 08:12

URI:

https://boris.unibe.ch/id/eprint/67450

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