IFN-γ transforms the transcriptomic landscape and triggers myeloid cell hyperresponsiveness to cause lethal lung injury.

ABSTRACT: Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes associated with inflammatory diseases. Further evidence

SUBMITTER: Verma AK 

PROVIDER: S-EPMC9530332 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature