Figure 2.

Non-infected versus infected injuries of the murine lungs. The release of DAMPs linked to a sterile induced-injury (ventilator-induced, acid aspiration, contusion, bleomycin injection, resection) in the pulmonary alveolus triggers an immune response consisting primarily of neutrophils and MФ, resulting in regeneration of the pulmonary epithelium. Alveolar MФ (GM-CSF, PPAR-γ and TFG-β), the first barrier to danger, phagocytose debris and dead cells. They prevent excessive inflammation, the formation of lesions and regulate surfactant. They can self-renew or be substituted by monocyte-derived MФ. The two types of interstitial MФ, located in part between the pulmonary epithelium and blood capillaries, enter the alveoli and help the alveolar MФ to respond to dangers. LYVE-1^low MHC Class II^high MФ are responsible for antigen presentation while LYVE-1^high MHC Class II^low help tissue repair. Upon tissue restoration, exchanges of O₂ and CO₂ through the capillaries return to normal. Injury in infectious conditions, for example caused by infection with Influenza A virus in mice, may impair the ability to regenerate. Alveolar MФ phagocytes debris, dead cells and the infectious agent. Alveolar MФ initially anti-inflammatory, adopt an inflammatory phenotype with the release of IFN-γ and TNF-α leading to the production of GM-CSF by epithelial cells, in turn activating dendritic cells (DC). Three weeks after infection of MФ, neutrophils and CD4⁺, CD8⁺ T cells are still present. Excessive inflammation with the persistent presence of pro-inflammatory MФ can eventually lead to extensive cell necrosis and the formation of non-functioning fibrous scar tissue. As a result, oxygen is no longer properly transferred to the blood capillaries and breathing difficulties may occur.