Prodigiosin targeting alveolar macrophages to mitigate the inflammatory response induced by H9N2 viral infection

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Respiratory viruses pose significant public health risks, with alveolar macrophages (AMs) crucial for antiviral defense.
• Dysregulated inflammation involving AMs can lead to severe pulmonary damage during viral infections.
• Prodigiosin (PDN) is known to modulate immune responses, but its specific role in AM regulation during viral respiratory infections is unclear.

Purpose of the Study:

• To investigate the therapeutic potential of prodigiosin (PDN) in mitigating respiratory viral infections.
• To elucidate the mechanisms by which PDN affects alveolar macrophages (AMs) during viral pneumonia.
• To evaluate PDN's efficacy in reducing inflammation and lung injury.

Main Methods:

• A mouse model of H9N2 avian influenza A virus (AIV) infection was utilized.
• Prodigiosin (PDN) treatment effects on morbidity, mortality, and pro-inflammatory cytokine levels were assessed.
• Histopathological lung damage, Wnt/β-catenin pathway activity, mitochondrial function, and AM senescence were analyzed.

Main Results:

• PDN significantly reduced morbidity and mortality in the AIV-infected mouse model.
• PDN treatment led to decreased pro-inflammatory cytokine production and mitigated lung histopathology.
• Mechanistically, PDN downregulated the Wnt/β-catenin pathway, preserved mitochondrial function, and inhibited AM senescence, especially in aged mice.

Conclusions:

• Prodigiosin (PDN) effectively alleviates inflammation and lung injury caused by respiratory viral infections by modulating alveolar macrophages (AMs).
• PDN demonstrates therapeutic potential for treating viral pneumonia, with particular promise for elderly individuals due to its effects on AM senescence.