Journal article

Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections

Antoine Roquilly, Hamish EG McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos

IMMUNITY | CELL PRESS | Published : 2017

Abstract

Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β. Paralyzed DCs secreted TGF-β and induced local Treg cell accumulation. They also expressed lower amounts of IRF4, a transcription factor associated with increased antigen-presentatio..

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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, F-44093, France [BRIF: BB-0033-00040]) and the Cytometry Facilty "Cytocell," University of Nantes. Funding: This work was funded with grants from the National Health and Medical Research Council of Australia (NHMRC) to J.A.V., the Sylvia and Charles Viertel Foundation (Senior Medical Research Fellowship to A.K.), the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. A.R. received grants from the Societe Francaise d'Anesthesie Reanimation and the Fondation des Gueules Cassees. Data and materials availability: Data can be accessed upon request from the server of the University of Melbourne.