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

• DOI: 10.1016/j.immuni.2017.02.016
• Publication Date: 2017-03-21T17:22:34Z
• Authors: Catherine Sabatel; Coraline Radermecker; Laurence Fievez; Genevieve Paulissen; Svetoslav Chakarov; Claudia Fernandes; Sabine Olivier; Marie Toussaint; Dimitri Pirottin; Xue Xiao; Pascale Quatresooz; Jean-Claude Sirard; Didier Cataldo; Laurent Gillet; Hicham Bouabe; Christophe J. Desmet; Florent Ginhoux; Thomas Marichal; Fabrice Bureau
• Keywords: DNA, Bacterial; MESH: Macrophages, Alveolar/immunology*; [SDV]Life Sciences [q-bio]; MESH: Flow Cytometry; MESH: Mice, Knockout; hygiene hypothesis; lung; TLR9; Mice; 03 medical and health sciences; 0302 clinical medicine; MESH: Oligodeoxyribonucleotides/immunology; MESH: Mice, Inbred C57BL; CpG; regulatory macrophages; MESH: Macrophage Activation/immunology; Macrophages, Alveolar; Hypersensitivity; Respiratory Hypersensitivity; Animals; MESH: Animals; MESH: Mice; Mice, Knockout; MESH: DNA, Bacterial/immunology*; Macrophages; MESH: Macrophages/immunology; asthma; Macrophage Activation; MESH: Chemotaxis, Leukocyte/immunology*; Flow Cytometry; 3. Good health; MESH: Spleen/immunology; [SDV] Life Sciences [q-bio]; Mice, Inbred C57BL; Chemotaxis, Leukocyte; Disease Models, Animal; Oligodeoxyribonucleotides; IL-10; CCR2; MESH: Hypersensitivity/immunology*; spleen; MESH: Disease Models, Animal; monocytes; Spleen; MESH: Respiratory Hypersensitivity/immunology*

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.