Ficolin A and ficolin B aggravate poly(I:C) secondary LPS stimulation-induced acute lung injury by modulating alveolar and interstitial macrophages

Respiratory viral Infection, represented by Influenza Virus, is easily followed by Bacterial infection, the main cause of death. Clinical studies have shown that even mild Influenza Virus infection followed by secondary Bacterial infection can mediate severe pneumonia and lung injury. In this study, mice were intranasally stimulated by polyinosinic-polycytidylic acid [poly(I:C)] followed by lipopolysaccharide (LPS) to simulate respiratory RNA virus secondary Gram-negative Bacterial infection. The results demonstrated that poly(I:C) followed by LPS stimulation induced more weight loss, worse lung pathological injury, additional recruitment of neutrophils and interstitial macrophages, and elevated expression of ficolin A/B in the lung neutrophils, alveolar and interstitial macrophages. Knockout of ficolin A/B alleviated the body weight loss, the lung pathological injury, and the pulmonary inflammatory score. Mechanically, knockout of ficolin A/B was associated with reduced interstitial macrophage recruitment and alveolar macrophage exhaustion. These results suggest that ficolin A/B is a potential therapeutic target for severe pneumonia induced by respiratory RNA virus secondary Gram-negative Bacterial infection.

Acute lung injury; Ficolin; Innate immune; Lipopolysaccharide (LPS); Polyinosinic-polycytidylic acid [poly(I:C)].