Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection.

Area of Science:

• Immunology
• Pulmonology
• Hepatology

Background:

• Systemic duress (sepsis, burns, trauma) increases susceptibility to secondary pneumonia.
• The hepatic acute-phase response (APR) is vital for limiting secondary lung infections.
• Understanding the lung-liver axis in inflammation is critical for host defense.

Purpose of the Study:

• To investigate liver-dependent lung reprogramming following systemic inflammation.
• To elucidate mechanisms of the lung-liver axis in preventing secondary pneumonia.

Main Methods:

• Wild-type and hepatocyte-specific STAT3-deficient mice (hepSTAT3-/-) were used.
• Endotoxemia was induced via LPS, followed by bacterial pneumonia (Escherichia coli).
• Transcriptional and proteomic analyses were performed on lung and airspace samples.

Main Results:

• Endotoxemia caused significant lung transcriptional changes, with nearly 2000 differentially expressed genes between genotypes.
• hepSTAT3-/- mice exhibited exaggerated lung immune activity and impaired cytokine responses.
• Liver-derived mediators substantially modified lung airspaces, impacting homeostasis.

Conclusions:

• Hepatic APR dramatically remodels the lungs after systemic inflammation, altering responses to subsequent stimuli.
• Intact liver function is critical for maintaining lung immunological responsiveness and preventing secondary infections.