Macrophage-derived lipocalin 2 drives severe pneumonia in SARS-CoV-2 infection

Publication date: Jul 02, 2025

Since the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), understanding the mechanisms underlying severe pneumonia has remained a major research challenge. By adapting the Beta variant to wild-type BALB/c mice, the team established a model of severe pneumonia, enabling detailed investigation into immune responses. By establishing a wild-type mouse model that closely mimics severe pneumonia, the researchers were able to uncover how the NLRP3-Lcn2 axis contributes to the pathogenesis. Targeting the NLRP3-Lcn2 axis may offer a new strategy to mitigate lung injury in severe respiratory infections. Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia. Among many inflammatory mediators, lipocalin 2 (Lcn2) has been increasingly associated with respiratory disease severity, yet its regulatory mechanisms and pathological consequences are not well defined. Functionally, Lcn2 was shown to amplify pulmonary inflammation by stimulating endothelial cells to express adhesion molecules (e. g., VCAM1), increasing neutrophil adhesion to endothelial cells, and weakening intercellular junctions.

Original Article