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19/05/2020

Congratulations to A.Roquilly and J.Poschmann for their paper published in Nature in Immunology

Sepsis and trauma cause inflammation and elevated susceptibility to hospital-acquired pneumonia. As phagocytosis by macro- phages 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 estab- lishment 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.

The paper has been accepted in Nature Immunology (18 May 2020)

Author List.

A.Roquilly, C.Jacqueline, M.Davieau, A.Mollé, A.Sadek, C.Fourgeux, P.Rooze, A.Broquet, B.Misme-Aucouturier, T.Chaumette, M.Vourc'h, R.Cinotti, N.Marec, V.Gautier, H.EG.G.McWilliam, F.Altare, J.Poschmann, J.A.Villadangos and K.Asehnoune