title: Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice.
abstract: The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions.
authors.affiliation: Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liège, Liège, Belgium.
authors.forename: Denis
authors.initials: D
authors.lastname: Bedoret
authors.forename: Hugues
authors.initials: H
authors.lastname: Wallemacq
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.forename: Christophe
authors.initials: C
authors.lastname: Desmet
authors.forename: Florence
authors.initials: F
authors.lastname: Quesada Calvo
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Henry
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Closset
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dewals
authors.forename: Caroline
authors.initials: C
authors.lastname: Thielen
authors.forename: Pascal
authors.initials: P
authors.lastname: Gustin
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.forename: Alain
authors.initials: A
authors.lastname: Vanderplasschen
authors.forename: Didier
authors.initials: D
authors.lastname: Cataldo
authors.forename: Pierre-Vincent
authors.initials: PV
authors.lastname: Drion
authors.forename: Muriel
authors.initials: M
authors.lastname: Moser
authors.forename: Pierre
authors.initials: P
authors.lastname: Lekeux
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
mesh_terms: D056704:Adaptive Immunity; D000485:Allergens / Q000633:toxicity; D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D008168:Lung / Q000166:cytology* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
chemical_list: D000485:Allergens; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D010047:Ovalbumin