Gsdmc-Mediated Pyroptosis: A Possible Mechanism for the Clearance of Worms
Researchers from West China School of Stomatology (WCSS), Sichuan University revealed that the up-regulated gasdermin C genes (Gsdmcs) family may be major effectors for type 2 responses in the gut and that Gsdmc-mediated pyroptosis may provide a conduit for the release of antiparasitic factors from enterocytes to facilitate the clearance of worms.
“Taste-like” tuft cells in the intestine trigger type 2 immunity in response to worm infection. The secretion of interleukin-13 (IL-13) from type 2 innate lymphoid cells (ILC2) represents a key step in the tuft cell–ILC2 cell–intestinal epithelial cell circuit that drives clearance of worms from the gut via type 2 immune responses. Hallmark features of type 2 responses include tissue remodeling, such as tuft and goblet cell expansion and villus atrophy, yet it remains unclear if additional molecular changes in the gut epithelium facilitate clearance of worms from the gut.
Gasdermin proteins are key effectors of pyroptosis, a highly inflammatory form of programmed cell death triggered by intracellular and extracellular pathogens, which represents a prominent antimicrobial response. Researchers identified pyroptosis-effector gasdermin C genes (Gsdmcs) as type 2 cytokine-regulated target genes in intestinal epithelial cells.
Upregulation of Gsdmcs in gut epithelial tissue of mice infected with N. brasiliensis.
Furthermore, they discovered that overexpression of Gsdmc2 triggered pyroptosis in HEK293 cells, intestinal organoid cultures and in vivo mouse models.
Lytic cell death in intestinal epithelium of wild-type mice infected with N. brasiliensis.
Their findings, published in the journal PNAS on July 21 2021, reveal that the involvement of lytic cell death in type 2 immunity is potentially mediated by Gsdmcs. And researchers infer that lytic cell death may help release antiparasitic factors from gut cells to fight these and other infectious agents.
Schematic illustration of lytic cell death upon N. brasiliensis (Nb) infection in wild-type mice.
The study’s first author is Ranhui Xi. Dr. Jiyao Li and Dr. Peihua Jiang are the study’s co-authors.
For more details, please click the link below.
https://www.pnas.org/doi/full/10.1073/pnas.2026307118
