Journal article

Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis

Antoine Roquilly, Cedric Jacqueline, Marion Davieau, Alice Molle, Abderrahmane Sadek, Cynthia Fourgeux, Paul Rooze, Alexis Broquet, Barbara Misme-Aucouturier, Tanguy Chaumette, Mickael Vourc'h, Raphael Cinotti, Nadege Marec, Vanessa Gauttier, Hamish EG McWilliam, Frederic Altare, Jeremie Poschmann, Jose A Villadangos, Karim Asehnoune

Nature Immunology | Nature Research | Published : 2020

Abstract

Sepsis and trauma cause inflammation and elevated susceptibility to hospital-acquired pneumonia. As phagocytosis by macrophages plays a critical role in the control of bacteria, we investigated the phagocytic activity of macrophages after resolution of inflammation. After resolution of primary pneumonia, murine alveolar macrophages (AMs) exhibited poor phagocytic capacity for several weeks. These paralyzed AMs developed from resident AMs that underwent an epigenetic program of tolerogenic training. Such adaptation was not induced by direct encounter of the pathogen but by secondary immunosuppressive signals established locally upon resolution of primary infection. Signal-regulatory protein α..

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Grants

Funding Acknowledgements

We thank the Biological Resource Centre for biobanking (CHU Nantes, Hotel Dieu, Centre de Ressources Biologiques (CRB), Nantes, France (BRIF: BB-0033-00040)), the Cytometry Facilty 'Cytocell', University of Nantes, and the Genomics and Bioinformatics Core Facility of Nantes (GenoBiRD, Biogenouest) for its technical support. OSE Immunotherapeutics provided Sirpa<SUP>-/-</SUP> mice and anti-Sirpa antibody but had no role in data analyses or revision of the manuscript. A.R. and J.P. received funding from the Region Pays de la Loire. This work was funded with grants from the National Health and Medical Research Council of Australia (NHMRC) to J.V., the Sylvia and Charles Viertel Foundation (Senior Medical Research Fellowship to A.K.), the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support scheme.