Adenovirus induces pediatric pneumonia via triggering macrophage polarization and IL-6 production via NF-κB activation.

Human adenovirus (HAdV) is one of major pathogens that causes acute respiratory infections in children. Pulmonary macrophages mediated pulmonary immune response is crucial in both host defense against HAdV and lung pathogenesis. However, the specific role of macrophage polarization in HAdV-induced lung injury remains unclear. Here, using bulk RNA-sequencing of bronchoalveolar lavage fluid (BALF) cells from children with HAdV pneumonia, we found that adenovirus infection upregulates the genes associated with macrophage polarization. Flow cytometry revealed a significantly higher proportion of M1 macrophages in severe cases compared to the non-severe cases. Mechanistically, in vitro infection of a human macrophage cell line demonstrated that HAdV directly induces M1 polarization and stimulates the production of inflammatory cytokine IL-6 via NF-κB activation. Our findings demonstrate that HAdV infection drives M1 macrophage polarization and IL-6 production through NF-κB signaling pathway, elucidating a key mechanism underlying the excessive inflammation and lung injury in severe HAdV infection.