title: Innate immunity contributes to cochlear adaptive immune responses.
abstract: Inner ear immune responses mediated by antigen-specific processes are thought to contribute to hearing loss in humans. Systemic activation of innate immunity contributes to immune responses in the central nervous system. We hypothesized that activation of innate immunity can prime the inner ear for adaptive immune responses and exacerbate disease. Mice were systemically immunized with antigen. Three weeks after initial antigen exposure, the antigen was injected intrathecally coincident with systemic injection of lipopolysaccharide (LPS), an activator of innate immunity. Responses were measured by quantifying the leukocyte infiltrate and cochlear IL-1beta expression. LPS stimulation markedly amplified the adaptive immune response to exogenous antigen in the inner ear. These data indicate that the cochlea is activated by systemic events that stimulate innate immunity and when antigen is present in the inner ear, a robust cochlear adaptive response is generated. If true in humans, this implies that priming may be an important component in the development of immune-mediated hearing loss.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, 9500 Gilman Dr., CA 92093-0666, USA.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Peter
authors.initials: P
authors.lastname: Billings
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Harris
authors.forename: Gary S
authors.initials: GS
authors.lastname: Firestein
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Keithley
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000276:immunology; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology*; D003051:Cochlea / Q000276:immunology*; D007758:Ear, Inner / Q000276:immunology; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000276:immunology*; D006433:Hemocyanins / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin