GSDMD Protects Intestinal Epithelial Cells Against Bacterial Infections Through Its N-terminal Activity Impacting Intestinal Immune Homeostasis

Overview

Journal J Biomed Res

Specialty General Medicine

Date 2024 May 29

PMID 38807373

Authors

Honghui Li

Jie Pu

Dongxue Yang

Lu Liu

Yingchao Hu

Shuo Yang

Bingwei Wang

Affiliations

Soon will be listed here.

Abstract

The intestinal mucosal barrier serves as a vital guardian for gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Recent studies have found the intricate roles of Gasdermin D (GSDMD), a key executioner of pyroptosis downstream of the inflammasome, within the intestine, including controlling colitis in intestinal macrophage and the regulatory function in goblet cell mucus secretion. Thus, the exact role and nature of GSDMD's regulatory function in maintaining intestinal immune homeostasis and defending against pathogens remain elucidation. Here, we uncover that GSDMD plays a key role in defending against intestinal infection, with high expression in intestinal epithelial and lamina propria myeloid cells. Our results show that GSDMD specifically acts in intestinal epithelial cells to fight the infection, independently of its effects on antimicrobial peptides or mucin secretion. Instead, the resistance is mediated through GSDMD's N-terminal fragments, highlighting its importance in intestinal immunity. However, the specific underlying mechanism of GSDMD N-terminal activity in protection against intestinal bacterial infections still needs further study to clarify in the future.

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