title: Lipopolysaccharide inhibits Th2 lung inflammation induced by house dust mite allergens in mice.
abstract: The complex biology of asthma compels the use of more relevant human allergens, such as house dust mite (HDM), to improve the translation of animal models into human asthma. LPS exposure is associated with aggravations of asthma, but the mechanisms remain unclear. Here, we studied the effects of increasing LPS doses on HDM-evoked allergic lung inflammation. To this end, mice were intranasally sensitized and challenged with HDM with or without increasing doses of LPS (0.001-10 μg). LPS dose-dependently inhibited HDM-induced eosinophil recruitment into the lungs and mucus production in the airways. LPS attenuated the production of Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) in HDM-challenged lungs, while enhancing the HDM-induced release of IL-17, IL-33, IFN-γ, and TNF-α. The shift toward a Th1 inflammatory response was further illustrated by predominant neutrophilic lung inflammation after LPS administration at higher doses. LPS did not influence HDM-induced plasma IgE concentrations. Although LPS did not significantly affect the activation of coagulation or complement in HDM-challenged lungs, it reduced HDM-initiated endothelial cell activation. This study is the first to provide insights into the effects of LPS in an allergic lung inflammation model making use of a clinically relevant allergen without a systemic adjuvant, revealing that LPS dose-dependently inhibits HDM-induced pulmonary Th2 responses.
authors.affiliation: Center of Infection and Immunity Amsterdam and Center of Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. j.d.deboer@amc.uva.nl
authors.forename: J
authors.initials: J
authors.lastname: Daan de Boer
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Regina
authors.initials: R
authors.lastname: de Beer
authors.forename: Marcel
authors.initials: M
authors.lastname: Schouten
authors.forename: Tijmen J
authors.initials: TJ
authors.lastname: Hommes
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.forename: Jaring S
authors.initials: JS
authors.lastname: van der Zee
authors.forename: Cornelis Van't
authors.initials: CV
authors.lastname: Veer
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D008070:Lipopolysaccharides; D007073:Immunoglobulin E