Low Doses of Radiation Increase the Immunosuppressive Profile of Lung Macrophages During Viral Infection and Pneumonia

Lydia Meziani (1) , Charlotte Robert (1, 2) , Marion Classe (1, 2) , Bruno da Costa (3) , Michele Mondini (1) , Céline Clémenson (1) , Alexia Alfaro (4) , Pierre Mordant (5, 6) , Samy Ammari (7, 8) , Ronan Le Goffic (3) , Eric Deutsch (1, 2)

1 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique
2 IGR - Institut Gustave Roussy
3 VIM (UR 0892) - Virologie et Immunologie Moléculaires
4 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
5 Service de Chirurgie Thoracique et Vasculaire [Hôpital Bichat]
6 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
7 BIOMAPS - LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay
8 Département d'imagerie médicale [Gustave Roussy]

Purpose: Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (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 of RT (0.5-1 Gray) decreased LPS-induced pneumonia, and increased the percentage of nerve- and airway-associated macrophages producing interleukin (IL) 10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses of 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 interferon γ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased. Conclusions: Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.

Domaines: Cancer

Lydia Meziani, Charlotte Robert, Marion Classe, Bruno da Costa, Michele Mondini, et al.. Low Doses of Radiation Increase the Immunosuppressive Profile of Lung Macrophages During Viral Infection and Pneumonia. International Journal of Radiation Oncology, Biology, Physics, 2021, 110 (5), pp.1283-1294. ⟨10.1016/j.ijrobp.2021.03.022⟩. ⟨hal-03401860⟩