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

Meziani, Lydia; Robert, Charlotte; Classe, Marion; Da Costa, Bruno; Mondini, Michele; Clémenson, Céline; Alfaro, Alexia; Mordant, Pierre; Ammari, Samy; Goffic, Ronan Le; Deutsch, Eric

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.