Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis
Antoine Roquilly
(1, 2, 3)
,
Cédric Jacqueline
(1)
,
Marion Davieau
(1)
,
Alice Mollé
(4, 5)
,
Abderrahmane Sadek
(4, 5, 6)
,
Cynthia Fourgeux
(4, 5)
,
Paul Rooze
(1, 2)
,
Alexis Broquet
(1)
,
Barbara Misme-Aucouturier
(1)
,
Tanguy Chaumette
(1)
,
Mickael Vourc’h
(1, 2)
,
Raphaël Cinotti
(2)
,
Nadège Marec
(7)
,
Vanessa Gauttier
(4, 5)
,
Hamish Mcwilliam
(3)
,
Frédéric Altare
(8)
,
Jérémie Poschmann
(9, 5)
,
Jose Villadangos
(3)
,
Karim Asehnoune
(1, 2)
1
EA 3826 -
Thérapeutiques cliniques et expérimentales des infections (EA 3826)
2 Anesthésie Réanimation chirurgicale [CHU Nantes]
3 University of Melbourne
4 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
5 ITUN - Institut de transplantation urologie-néphrologie
6 UMI - جامعة مولاي إسماعيل = Université Moulay Ismaïl
7 CRCINA-CYTOCELL - Plateforme CYTOCELL Nantes
8 CRCINA-ÉQUIPE 5 - Host-Pathogen Interactions in the Regulation of Immune Responses
9 Team 1 - U1064 Inserm - CRTI - Dendritic cells and immunoregulation in transplantation and immunopathology
2 Anesthésie Réanimation chirurgicale [CHU Nantes]
3 University of Melbourne
4 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
5 ITUN - Institut de transplantation urologie-néphrologie
6 UMI - جامعة مولاي إسماعيل = Université Moulay Ismaïl
7 CRCINA-CYTOCELL - Plateforme CYTOCELL Nantes
8 CRCINA-ÉQUIPE 5 - Host-Pathogen Interactions in the Regulation of Immune Responses
9 Team 1 - U1064 Inserm - CRTI - Dendritic cells and immunoregulation in transplantation and immunopathology
Antoine Roquilly
- Fonction : Auteur
- PersonId : 767046
- ORCID : 0000-0002-1029-6242
- IdRef : 14637939X
Alexis Broquet
- Fonction : Auteur
- PersonId : 779030
- ORCID : 0000-0002-6635-9601
- IdRef : 097532061
Raphaël Cinotti
- Fonction : Auteur
- PersonId : 949133
- ORCID : 0000-0001-9217-8532
- IdRef : 140188363
Frédéric Altare
- Fonction : Auteur
- PersonId : 182600
- IdHAL : frederic-altare
- ORCID : 0000-0002-5077-4616
- IdRef : 110960645
Résumé
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.