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Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages

Immunity (Cambridge, Mass.), 2017-03, Vol.46 (3), p.457-473 [Peer Reviewed Journal]

2017 Elsevier Inc. ;Copyright © 2017 Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Mar 21, 2017 ;Distributed under a Creative Commons Attribution 4.0 International License ;ISSN: 1074-7613 ;ISSN: 1097-4180 ;EISSN: 1097-4180 ;DOI: 10.1016/j.immuni.2017.02.016 ;PMID: 28329706

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Title:
Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages
Author: Sabatel, Catherine ; Radermecker, Coraline ; Fievez, Laurence ; Paulissen, Genevieve ; Chakarov, Svetoslav ; Fernandes, Claudia ; Olivier, Sabine ; Toussaint, Marie ; Pirottin, Dimitri ; Xiao, Xue ; Quatresooz, Pascale ; Sirard, Jean-Claude ; Cataldo, Didier ; Gillet, Laurent ; Bouabe, Hicham ; Desmet, Christophe J. ; Ginhoux, Florent ; Marichal, Thomas ; Bureau, Fabrice
Subjects: Allergens ; Allergies ; Animals ; Asthma ; Bacteria ; Biochemistry, biophysics & molecular biology ; Biochimie, biophysique & biologie moléculaire ; Bone marrow ; CCR2 ; Chemotaxis, Leukocyte - immunology ; CpG ; Dendritic cells ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; DNA, Bacterial - immunology ; Emigration ; Exposure ; Flow Cytometry ; hygiene hypothesis ; Hypersensitivity - immunology ; Hypotheses ; IL-10 ; Immunology ; Inflammation ; Life Sciences ; lung ; Lungs ; Macrophage Activation - immunology ; Macrophages ; Macrophages - immunology ; Macrophages, Alveolar - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes ; Morphology ; Oligodeoxyribonucleotides - immunology ; regulatory macrophages ; Respiratory Hypersensitivity - immunology ; Risk reduction ; Rodents ; Sciences du vivant ; Spleen ; Spleen - immunology ; TLR9
Is Part Of: Immunity (Cambridge, Mass.), 2017-03, Vol.46 (3), p.457-473
Description: 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. [Display omitted] •Exposure to bacterial CpG DNA (CpG) expands regulatory lung interstitial macrophages (IMs)•Transfer of WT but not Il10−/− IMs protects from allergen-induced airway inflammation•CpG-induced IMs arise from local and splenic reservoir monocytes•Migration of regulatory IM precursors to the lung does not require CCR2 Exposure to unmethylated CpG DNA (CpG) from bacteria is associated with a reduced risk of developing asthma. Sabatel et al. find that CpG exposure leads to higher numbers of lung interstitial macrophages that prevent allergic inflammation through the production of the regulatory cytokine interleukin-10.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1074-7613
ISSN: 1097-4180
EISSN: 1097-4180
DOI: 10.1016/j.immuni.2017.02.016
PMID: 28329706
Source: Cell Press Free Archives
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Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages

2017 Elsevier Inc. ;Copyright © 2017 Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Mar 21, 2017 ;Distributed under a Creative Commons Attribution 4.0 International License ;ISSN: 1074-7613 ;ISSN: 1097-4180 ;EISSN: 1097-4180 ;DOI: 10.1016/j.immuni.2017.02.016 ;PMID: 28329706

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