Gasdermin D is the only Gasdermin that provides protection against acute Salmonella gut infection in mice.

Details

Serval ID
serval:BIB_5D7AB13847DD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gasdermin D is the only Gasdermin that provides protection against acute Salmonella gut infection in mice.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Fattinger S.A., Maurer L., Geiser P., Bernard E.M., Enz U., Ganguillet S., Gül E., Kroon S., Demarco B., Mack V., Furter M., Barthel M., Pelczar P., Shao F., Broz P., Sellin M.E., Hardt W.D.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
28/11/2023
Peer-reviewed
Oui
Volume
120
Number
48
Pages
e2315503120
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Gasdermins (GSDMs) share a common functional domain structure and are best known for their capacity to form membrane pores. These pores are hallmarks of a specific form of cell death called pyroptosis and mediate the secretion of pro-inflammatory cytokines such as interleukin 1β (IL1β) and interleukin 18 (IL18). Thereby, Gasdermins have been implicated in various immune responses against cancer and infectious diseases such as acute Salmonella Typhimurium (S.Tm) gut infection. However, to date, we lack a comprehensive functional assessment of the different Gasdermins (GSDMA-E) during S.Tm infection in vivo. Here, we used epithelium-specific ablation, bone marrow chimeras, and mouse lines lacking individual Gasdermins, combinations of Gasdermins or even all Gasdermins (GSDMA1-3C1-4DE) at once and performed littermate-controlled oral S.Tm infections in streptomycin-pretreated mice to investigate the impact of all murine Gasdermins. While GSDMA, C, and E appear dispensable, we show that GSDMD i) restricts S.Tm loads in the gut tissue and systemic organs, ii) controls gut inflammation kinetics, and iii) prevents epithelium disruption by 72 h of the infection. Full protection requires GSDMD expression by both bone-marrow-derived lamina propria cells and intestinal epithelial cells (IECs). In vivo experiments as well as 3D-, 2D-, and chimeric enteroid infections further show that infected IEC extrusion proceeds also without GSDMD, but that GSDMD controls the permeabilization and morphology of the extruding IECs, affects extrusion kinetics, and promotes overall mucosal barrier capacity. As such, this work identifies a unique multipronged role of GSDMD among the Gasdermins for mucosal tissue defense against a common enteric pathogen.
Keywords
immunology, microbiology, pathogen, pyroptosis
Pubmed
Open Access
Yes
Create date
23/11/2023 14:56
Last modification date
01/12/2023 8:30
Usage data