Frontiers in cell and developmental biology
TREM-1 deficiency attenuates RIPK3/MLKL-associated epithelial injury in Klebsiella pneumoniae-induced acute lung injury
By Zhang W, Meng S, Huang J and 4 others.
Abstract
Background
Klebsiella pneumoniae (KP)-induced acute lung injury involves excessive myeloid inflammation, epithelial barrier disruption, and inflammatory cell death. Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies innate immune responses, whereas receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) signaling contributes to membrane injury. Their relationship during bacterial lung infection remains incompletely understood.
Methods
KP-induced acute lung injury was established in wild-type and Trem1-deficient mice, and GSK872 was administered prophylactically to inhibit RIPK3. Lung histopathology, inflammatory mediators, and RIPK3/MLKL activation were assessed. Two human lung single-cell RNA-sequencing datasets containing non-fibrotic and fibrotic tissues were analyzed as cross-disease, hypothesis-generating reference cohorts. In vitro, conditioned medium from KP-stimulated THP-1-derived macrophage-like cells was applied to BEAS-2B epithelial cells; macrophage TREM-1 was blocked with LP17, and epithelial RIPK3 was silenced using siRNA.