ChemR23 Dampens Lung Inflammation and Enhances Anti-viral Immunity in a Mouse Model of Acute Viral Pneumonia

PLoS Pathogens

Olivier De Henau¹  David Communi²  Benjamin Bondue³  Patricia de Nadai³  Daniel Desmecht³  Stéphanie Glineur³  Souphalone Luangsay³  Frédéric Van Gool³  Paul De Vuyst⁴  Olivier Vosters⁵  Marc Parmentier⁵ 

[1] Département de Pathologie, Faculté de Médecine Vétérinaire, Université de Liège, Liège, Belgium;Euroscreen SA, Brussels, Belgium;Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium;Laboratoire de Physiologie Animale, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium;Service de Pneumologie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

关键词: Mouse models;    Dendritic cells;    Inflammation;    Respiratory infections;    Neutrophils;    Enzyme-linked immunoassays;    Immune response;    T cells;   

DOI  :  10.1371/journal.ppat.1002358

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23−/− mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23−/− mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies.

【 授权许可】

CC BY