title: Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia.
abstract: Respiratory viral infections are associated with an increased risk of asthma, but how acute Th1 antiviral immune responses lead to chronic inflammatory Th2 disease remains undefined. We define a novel pathway that links transient viral infection to chronic lung disease with dendritic cell (DC) expression of the high-affinity IgE receptor (FcepsilonRIalpha). In a mouse model of virus-induced chronic lung disease, in which Sendai virus triggered a switch to persistent mucous cell metaplasia and airway hyperreactivity after clearance of replicating virus, we found that FceRIa(-/-) mice no longer developed mucous cell metaplasia. Viral infection induced IgE-independent, type I IFN receptor-dependent expression of FcepsilonRIalpha on mouse lung DCs. Cross-linking DC FcepsilonRIalpha resulted in the production of the T cell chemoattractant CCL28. FceRIa(-/-) mice had decreased CCL28 and recruitment of IL-13-producing CD4(+) T cells to the lung after viral infection. Transfer of wild-type DCs to FceRIa(-/-) mice restored these events, whereas blockade of CCL28 inhibited mucous cell metaplasia. Therefore, lung DC expression of FcepsilonRIalpha is part of the antiviral response that recruits CD4(+) T cells and drives mucous cell metaplasia, thus linking antiviral responses to allergic/asthmatic Th2 responses.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA. wheeze@allergist.com
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Grayson
authors.forename: Dorothy
authors.initials: D
authors.lastname: Cheung
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rohlfing
authors.forename: Robert
authors.initials: R
authors.lastname: Kitchens
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Spiegel
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tucker
authors.forename: John T
authors.initials: JT
authors.lastname: Battaile
authors.forename: Yael
authors.initials: Y
authors.lastname: Alevy
authors.forename: Le
authors.initials: L
authors.lastname: Yan
authors.forename: Eugene
authors.initials: E
authors.lastname: Agapov
authors.forename: Edy Y
authors.initials: EY
authors.lastname: Kim
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000276:immunology*; D020545:Respiratory Mucosa / Q000473:pathology* / Q000821:virology; D019562:Viral Load; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D017455:Receptors, IgE