Epithelial inflammasomes, gasdermins, and mucosal inflammation – Lessons from Salmonella and Shigella infected mice


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Date

2023-08-08

Publication Type

Review Article

ETH Bibliography

yes

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Abstract

Besides its crucial function in nutrient absorbance and as barrier against the microbiota, the gut epithelium is essential for sensing pathogenic insults and mounting of an appropriate early immune response. In mice, the activation of the canonical NAIP/NLRC4 inflammasome is critical for the defense against enterobacterial infections. Activation of the NAIP/NLRC4 inflammasome triggers the extrusion of infected intestinal epithelial cells (IEC) into the gut lumen, concomitant with inflammasome-mediated lytic cell death. The membrane permeabilization, a hallmark of pyroptosis, is caused by the pore-forming proteins called gasdermins (GSDMs). Recent work has revealed that NAIP/NLRC4-dependent extrusion of infected IECs can, however, also be executed in the absence of GSDMD. In fact, several reports highlighted that various cell death pathways (e.g., pyroptosis or apoptosis) and unique mechanisms specific to particular infection models and stages of gut infection are in action during epithelial inflammasome defense against intestinal pathogens. Here, we summarize the current knowledge regarding the underlying mechanisms and speculate on the putative functions of the epithelial inflammasome activation and cell death, with a particular emphasis on mouse infection models for two prominent enterobacterial pathogens, Salmonella Typhimurium and Shigella flexneri.

Publication status

published

Editor

Book title

Volume

70

Pages / Article No.

101812

Publisher

Academic Press

Event

Edition / version

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Date collected

Date created

Subject

Pyroptosis; Epithelial cells; Salmonella; Gasdermins; Cell death

Organisational unit

03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich check_circle

Notes

Funding

192567 - Mechanisms controlling the Salmonella Typhimurium gut infection (SNF)

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