Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages.
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.
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium.
Catherine
C
Sabatel
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium.
Coraline
C
Radermecker
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium.
Laurence
L
Fievez
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium.
Genevieve
G
Paulissen
Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore 138648, Singapore.
Svetoslav
S
Chakarov
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium.
Claudia
C
Fernandes
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium.
Sabine
S
Olivier
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
Marie
M
Toussaint
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium.
Dimitri
D
Pirottin
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.
Xue
X
Xiao
Centre de Recherche sur les Protéines Prion, Department of Human Histology, University of Liège, 4000 Liège, Belgium.
Pascale
P
Quatresooz
INSERM U1019, CNRS UMR 8204, Center for Infection and Immunity of Lille, University of Lille, CHU Lille, Institut Pasteur de Lille, 59000 Lille, France.
Jean-Claude
JC
Sirard
Laboratory of Tumor and Developmental Biology, GIGA Research, University of Liège, 4000 Liège, Belgium.
Didier
D
Cataldo
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.
Laurent
L
Gillet
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK.
Hicham
H
Bouabe
Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium.
Christophe J
CJ
Desmet
Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore 138648, Singapore.
Florent
F
Ginhoux
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.
Thomas
T
Marichal
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.
Fabrice
F
Bureau
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013154:Spleen / Q000276:immunology
C408982:CPG-oligonucleotide; D004269:DNA, Bacterial; D009838:Oligodeoxyribonucleotides
CCR2; CpG; IL-10; TLR9; asthma; hygiene hypothesis; lung; monocytes; regulatory macrophages; spleen