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Journal Articles Nature Immunology Year : 2020

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

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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 (SIRPα) played a critical role in the establishment of the microenvironment that induced tolerogenic training. In humans with systemic inflammation, AMs and also circulating monocytes still displayed alterations consistent with reprogramming six months after resolution of inflammation. Antibody blockade of SIRPα restored phagocytosis in monocytes of critically ill patients in vitro, which suggests a potential strategy to prevent hospital-acquired pneumonia.
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Dates and versions

inserm-02632161 , version 1 (27-05-2020)

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Antoine Roquilly, Cédric Jacqueline, Marion Davieau, Alice Mollé, Abderrahmane Sadek, et al.. Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis. Nature Immunology, 2020, 21 (6), pp.636-648. ⟨10.1038/s41590-020-0673-x⟩. ⟨inserm-02632161⟩
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