Low doses of radiation increase the immunosuppressive profile of lung macrophages during viral infection and pneumonia.

Abstract Purpose severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe COVID-19. Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown. Methods and materials here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and Toll- like receptor (TLR)-3 stimulation in human lung macrophages. Results low doses RT (0.5-1Gy) decreased LPS induced pneumonia, and increased the percentage of Nerve- and Airway- associated Macrophages (NAMs) producing IL-10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses RT increased IL-10 production by infiltrating immune cells into the lung. Irradiation of TLR-3 ligand-stimulated human lung macrophages ex vivo increased IL-10 secretion and decreased IFNγ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased. Conclusion our data highlight one of the mechanisms by which low doses RT regulate lung inflammation and skew lung macrophages towards an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses RT, as for COVID-19-induced ARDS.