β-Glucan reprograms alveolar macrophages via neutrophil/IFNγ axis in a murine model of lung injury
Renaud Prével, Erwan Pernet, Kim A. Tran, Abderrahmane Sadek, Mina Sadeghi, Elizabeth Lapshina, Leonardo F. Jurado, Arnold S. Kristof, Mohiéddine Moumni, Jérémie Poschmann, Maziar Divangahi
Abstract
Alveolar macrophages (AMs) reside in the lower airways and play a crucial role in lung health and response to sterile inflammation and infections. AMs possess remarkable adaptability to different environmental challenges that can persist through their memory capacity (trained immunity). β-Glucan has been characterized as a potent inducer of central trained immunity by reprogramming haematopoietic stem cells in the bone marrow. In the present study, we show that systemic administration of β-glucan in mice induces peripheral trained immunity by reprogramming AMs in the lungs, in a Dectin1-independent manner. We furthermore demonstrate that AM reprogramming at both the transcriptional and metabolic levels exacerbate lung injury following bacterial (lipopolysaccharide) or viral (polyI:C) challenges via a neutrophil/IFN-γ-dependent manner. These findings identify an additional facet of β-glucan in trained immunity involving AM reprogramming and shed light on the potential detrimental effects of trained immunity.