title: Both hemopoietic and resident cells are required for MyD88-dependent pulmonary inflammatory response to inhaled endotoxin.
abstract: Inhaled endotoxin induces an inflammatory response that contributes to the development and severity of asthma and other forms of airway disease. Here, we show that inhaled endotoxin-induced acute bronchoconstriction, TNF, IL-12p40, and KC production, protein leak, and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecule MyD88. Bronchoconstriction, inflammation, and protein leak are normal in Toll/IL-1R domain-containing adaptor inducing IFN-beta-deficient mice. MyD88 is involved in TLR, but also in IL-1R-associated kinase 1-mediated IL-1R and -18R signaling. We exclude a role for IL-1 and IL-18 pathways in this response, as IL-1R1 and caspase-1 (ICE)-deficient mice develop lung inflammation while TLR4-deficient mice are unresponsive to inhaled LPS. Significantly, using bone marrow chimera, we demonstrate that both hemopoietic and resident cells are necessary for a full MyD88-dependent response to inhaled endotoxin; bronchoconstriction depends on resident cells while cytokine secretion is mediated by hemopoietic cells.
authors.affiliation: Centre National de la Recherche Scientifique Transgenose Institute, Orleans, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noulin
authors.forename: Valérie F J
authors.initials: VF
authors.lastname: Quesniaux
authors.forename: Silvia
authors.initials: S
authors.lastname: Schnyder-Candrian
authors.forename: Bruno
authors.initials: B
authors.lastname: Schnyder
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maillet
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: B Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Couillin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016084:Bronchoconstriction / Q000187:drug effects*; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88; D009504:Neutrophils / Q000187:drug effects; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic