TY - JOUR T1 - Low doses of radiation increase the immunosuppressive profile of lung macrophages during viral infection and pneumonia JF - bioRxiv DO - 10.1101/2020.05.11.077651 SP - 2020.05.11.077651 AU - Lydia Meziani AU - Charlotte Robert AU - Marion Classe AU - Bruno Da Costa AU - Michele Mondini AU - Céline Clemenson AU - Pierre Mordant AU - Samy Ammari AU - Ronan Le Goffic AU - Eric Deutsch Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/14/2020.05.11.077651.abstract N2 - Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe COVID-19. Recently, early clinical data reported the efficacy of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown. Here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and Tolllike receptor (TLR)-3 stimulation in human lung macrophages. Low doses RT (0.5-1 Gy) 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. 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 the preclinical rationale for the use and for the optimization of low doses RT in situations such as COVID-19-induced ARDS.Competing Interest StatementDeclarations: Competing interests: The authors declare that they have no potential conflicts of interest related to this work. E. DEUTSCH reports grants and personal fees from ROCHE GENENTECH, grants from SERVIER, grants from ASTRAZENECA, grants and personal fees from MERCK SERONO, grants from BMS, grants from MSD, outside the submitted work ER -