1417-ZBP1-Driven Macrophage Pyroptosis in Sepsis

This study investigates how ZBP1-driven macrophage pyroptosis worsens sepsis-induced acute lung injury by damaging the pulmonary epithelium. Through single-cell RNA sequencing of human and mouse samples, researchers identified a specific group of pyroptosis-associated macrophages that expands during severe sepsis. These macrophages interact with the NLRP3 inflammasome to trigger cell death and release inflammatory cytokines like TNF-α and IL-1β. These signals disrupt the mitochondrial function and barrier integrity of alveolar type II epithelial cells, leading to organ dysfunction. Notably, removing the ZBP1 protein in animal models successfully reduced this harmful inflammatory crosstalk and protected lung tissue. These findings highlight ZBP1 as a potential therapeutic target for restoring immune balance and preventing mortality in septic patients.

References:

• Zhou F, Tian H, Wang H, et al. ZBP1-driven pyroptosis-associated alveolar macrophages exacerbate epithelial dysfunction in sepsis[J]. Cell Death & Disease, 2026.