Re. AZD1419 (and DV281?), phase II trial for latter is being routinely updated at ctdotgov.....
Immunity. 2017 Mar 21;46(3):457-473. doi: 10.1016/j.immuni.2017.02.016.
Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages.
Sabatel C1, Radermecker C1, Fievez L2, Paulissen G2, Chakarov S3, Fernandes C2, Olivier S2, Toussaint M4, Pirottin D1, Xiao X5, Quatresooz P6, Sirard JC7, Cataldo D8, Gillet L5, Bouabe H9, Desmet CJ2, Ginhoux F3, Marichal T10, Bureau F11.
1
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium.
2
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium.
3
Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore 138648, Singapore.
4
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
5
Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium; Laboratory of Immunology-Vaccinology, Fundamental and Applied Research for Animals & Health, University of Liège, 4000 Liège, Belgium.
6
Centre de Recherche sur les Protéines Prion, Department of Human Histology, University of Liège, 4000 Liège, Belgium.
7
INSERM U1019, CNRS UMR 8204, Center for Infection and Immunity of Lille, University of Lille, CHU Lille, Institut Pasteur de Lille, 59000 Lille, France.
8
Laboratory of Tumor and Developmental Biology, GIGA Research, University of Liège, 4000 Liège, Belgium.
9
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK.
10
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium. Electronic address: t.marichal@ulg.ac.be.
11
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium; Walloon Excellence in Life Sciences and Biotechnology, Wallonia, Belgium. Electronic address: fabrice.bureau@ulg.ac.be.
Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow. Using a mouse model of allergic airway inflammation, we found that adoptive transfer of IMs isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. IM-mediated protection was dependent on IL-10, given that Il10-/- CpG-induced IMs lacked regulatory effects. Thus, the expansion of regulatory lung IMs upon exposure to CpG might underlie the reduced risk of asthma development associated with a microbe-rich environment. |
