title: Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity.
abstract: Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (T(H)2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)-IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.
authors.affiliation: Division of Immunology and Allergy, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ya-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Lee A
authors.initials: LA
authors.lastname: Albacker
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumgarth
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Smith
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: Dekruyff
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D002352:Carrier Proteins; C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D007378:Interleukins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse