Monitoring the Cascade\nof Monocyte-Derived Macrophages\nto Influenza Virus Infection in Human Alveolus Chips

Respiratory viruses ravage the world and seriously threaten\npeople’s\nhealth. Despite intense research efforts, the immune mechanism underlying\nrespiratory virus-induced acute lung injury (ALI) and pulmonary fibrosis\n(PF) has not been fully elucidated. Here, the cascade of monocyte-derived\nmacrophages to influenza A virus infection is monitored on an optimized\nhuman alveolus chip to reveal the role of macrophages in the development\nof ALI and PF. We find that viral infection causes damage to the alveolar\nair–liquid barrier and the release of inflammatory cytokines,\nwhich induce the M0 macrophages to gather and polarize to the M1 phenotype\nat the damaged site through recruitment, adhesion, migration, and\nactivation, leading to ALI. Afterward, M1 macrophages polarize into\nthe M2 phenotype, and then transform into myofibroblasts, followed\nby enhanced secretion of various anti-inflammatory cytokines and profibrotic\ncytokines, to promote PF. Our study provides an insight into the pathogenesis\nof virus-induced ALI and PF, which will assist in the development\nof therapeutic strategies and drugs for treating influenza and other\nrespiratory virus infections.