title: Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity.
abstract: Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. The protective effect was associated with the preferential expansion of CD4-CD8-, but not CD4+, NKT cells and required T-bet and TLR7. Adoptive transfer of this cell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3+ (Foxp3+) Treg cell population. Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d-restricted fashion. These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.
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: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumgarth
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Shin
authors.initials: S
authors.lastname: Endo
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Janneke
authors.initials: J
authors.lastname: Maaskant
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitano
authors.forename: Abel
authors.initials: A
authors.lastname: Singh
authors.forename: Apoorva
authors.initials: A
authors.lastname: Bhatt
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Peter
authors.initials: P
authors.lastname: van den Elzen
authors.forename: Ben
authors.initials: B
authors.lastname: Appelmelk
authors.forename: Richard W
authors.initials: RW
authors.lastname: Franck
authors.forename: Guangwu
authors.initials: G
authors.lastname: Chen
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: Michio
authors.initials: M
authors.lastname: Shimamura
authors.forename: Petr
authors.initials: P
authors.lastname: Illarionov
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000833:Animals, Suckling; D001249:Asthma / Q000276:immunology / Q000517:prevention & control; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000150:complications / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018448:Models, Immunological; D055611:Natural Killer T-Cells / Q000145:classification / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006017:Glycolipids; D010047:Ovalbumin