title: Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
abstract: To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.
authors.affiliation: Department of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Edy Y
authors.initials: EY
authors.lastname: Kim
authors.forename: John T
authors.initials: JT
authors.lastname: Battaile
authors.forename: Anand C
authors.initials: AC
authors.lastname: Patel
authors.forename: Yingjian
authors.initials: Y
authors.lastname: You
authors.forename: Eugene
authors.initials: E
authors.lastname: Agapov
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Grayson
authors.forename: Loralyn A
authors.initials: LA
authors.lastname: Benoit
authors.forename: Derek E
authors.initials: DE
authors.lastname: Byers
authors.forename: Yael
authors.initials: Y
authors.lastname: Alevy
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tucker
authors.forename: Suzanne
authors.initials: S
authors.lastname: Swanson
authors.forename: Rose
authors.initials: R
authors.lastname: Tidwell
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Tyner
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Morton
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Deepika
authors.initials: D
authors.lastname: Polineni
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Patterson
authors.forename: Reto A
authors.initials: RA
authors.lastname: Schwendener
authors.forename: John D
authors.initials: JD
authors.lastname: Allard
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D055271:Mucin 5AC; D009077:Mucins / Q000032:analysis / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D029082:Sendai virus / Q000502:physiology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018793:Interleukin-13; C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger