[en] The lung is constantly exposed to airborne pathogens and particles that can cause alveolar damage. Hence, appropriate repair responses are essential for gas exchange and life. Here, we deciphered the spatiotemporal trajectory and function of an atypical population of macrophages after lung injury. Post-influenza A virus (IAV) infection, short-lived monocyte-derived Ly6G-expressing macrophages (Ly6G+ Macs) were recruited to the alveoli of lung perilesional areas. Ly6G+ Macs engulfed immune cells, exhibited a high metabolic potential, and clustered with alveolar type 2 epithelial cells (AT2s) in zones of active epithelial regeneration. Ly6G+ Macs were partially dependent on granulocyte-macrophage colony-stimulating factor and interleukin-4 receptor signaling and were essential for AT2-dependent alveolar regeneration. Similar macrophages were recruited in other models of injury and in the airspaces of lungs from patients with suspected pneumonia. This study identifies perilesional alveolar Ly6G+ Macs as a spatially restricted, short-lived macrophage subset promoting epithelial regeneration postinjury, thus representing an attractive therapeutic target for treating lung damage.
Disciplines :
Life sciences: Multidisciplinary, general & others
Abinet, Joan ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF)
Maréchal, Pauline; Laboratory of Immunophysiology, GIGA Institute, University of Liège, Liège, Belgium ; Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
Meunier, Margot ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
de Meeûs, Constance; Faculty of Veterinary Medicine, University of Liège, Liège, Belgium ; Department of Pathology, FARAH Institute, University of Liège, Liège, Belgium
Janssen, Pierre ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Médecine vétérinaire comparée
Dourcy, Mickael ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Thiry, Marc ; Université de Liège - ULiège > Département des sciences de la vie > Service collectif des enseignements de biologie en bachelier
Schneider, Christoph ; Institute of Physiology, University of Zurich, Zurich, Switzerland
Machiels, Bénédicte ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Hidalgo, Andres; Area of Cell & Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain ; Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
Ginhoux, Florent ; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China ; Inserm U1015, Gustave Roussy, Bâtiment de Médecine Moléculaire, Villejuif, France ; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore ; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore
Dewals, Benjamin G ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Immunologie vétérinaire
Guiot, Julien ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Marichal, Thomas ✱; Université de Liège - ULiège > GIGA > GIGA I3 - Immunophysiology ; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
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