Neutrophil extracellular traps mediate severe lung injury induced by influenza A virus H1N1 in mice coinfected with Staphylococcus aureus.

Influenza virus and bacterial infection contributed to massive morbidity and mortality. However, the underlying mechanisms were poorly understood. A coinfected model was generating by using sublethal doses of influenza A virus H1N1 A/FM/1/47(H1N1) and methicillin-resistant Staphylococcus aureus (MRSA). Further, the model was optimized to achieve the highest peak of mortality initiated by intranasal infection with 0.2LD H1N1 and 0.16LD MRSA at 3 days interval. Excessive neutrophil recruitment, accompanied by high levels of inflammatory cytokines and chemokines, and increased bacterial and viral load were observed in coinfected mice. Under the inflammatory environments triggered by H1N1 and MRSA, the excessive neutrophil recruitment led to the formation of neutrophil extracellular traps (NETs), associated with severe inflammation and vascular endothelial injury. Importantly, the severity of lung injury could be alleviated by treatment with DNase I or a selective neutrophil elastase inhibitor (NEi). Therefore, our data suggested that excessive neutrophil recruitment and NETs formation contributed to severe inflammation and acute lung injury in coinfected animals.