Alveolar Macrophages Participate in the Promotion of Influenza Virus Infection by Aflatoxin B1 at an Early Stage

Aflatoxin B1 (AFB1), one of the most common environmental mycotoxin contaminations in food and feed, poses significant threats to human and animal health. Our previous study indicated that even non-toxic AFB1 concentrations could promote influenza virus replication and induce influenza virus-infected alveolar macrophages polarizing from M1 (immunostimulatory phenotype) to M2 (immunosuppressive phenotype) over time. However, whether AFB1 promotes influenza replication via modulating the polarization of alveolar macrophages is unknown. Here, we specifically depleted alveolar macrophages using clodronate-containing liposomes in swine influenza virus (SIV)-infected mice to explore the mechanism the promotion of SIV replication by AFB1. The results show that the depletion of alveolar macrophages significantly alleviated the AFB1-induced weight loss, inflammatory responses, and lung and immune organ damage of the SIV-infected mice after 14 days and greatly diminished the AFB1-promoted SIV replication. In contrast, the depletion of alveolar macrophages did not alleviate the AFB1-induced weight loss, and lung and immune organ damage of the SIV-infected mice after 28 days and slightly diminished the AFB1-promoted SIV replication. Collectively, the data indicate that alveolar macrophages play a crucial role the promotion of SIV infection by AFB1 in the early rather than late stage, and AFB1 can promote SIV replication by inducing alveolar macrophages to polarize towards M1 macrophages. This research provides novel targets for reducing the risk of AFB1-promoted influenza virus infection.