title: Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease.
abstract: Deleterious responses to pathogens during infancy may contribute to infection and associated asthma. Chlamydia respiratory infections in early life are common causes of pneumonia and lead to reduced lung function and asthma. We investigated the role of interleukin-13 (IL-13) in promoting early-life Chlamydia respiratory infection, infection-induced airway hyperresponsiveness (AHR), and severe allergic airway disease (AAD). Infected infant Il13(-/-) mice had reduced infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly, infection of wild-type (WT) mice did not increase IL-13 production but reduced IL-13Rα2 decoy receptor levels compared with sham-inoculated controls. Infection of WT but not Il13(-/-) mice induced persistent AHR. Infection and associated pathology were restored in infected Il13(-/-) mice by reconstitution with IL-13. Stat6(-/-) mice were also largely protected. Neutralization of IL-13 during infection prevented subsequent infection-induced severe AAD. Thus, early-life Chlamydia respiratory infection reduces IL-13Rα2 production, which may enhance the effects of constitutive IL-13 and promote more severe infection, persistent AHR, and AAD.
authors.affiliation: Center for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Starkey
authors.forename: A T
authors.initials: AT
authors.lastname: Essilfie
authors.forename: J C
authors.initials: JC
authors.lastname: Horvat
authors.forename: R Y
authors.initials: RY
authors.lastname: Kim
authors.forename: D H
authors.initials: DH
authors.lastname: Nguyen
authors.forename: K W
authors.initials: KW
authors.lastname: Beagley
authors.forename: J
authors.initials: J
authors.lastname: Mattes
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
authors.forename: P M
authors.initials: PM
authors.lastname: Hansbro
mesh_terms: D017668:Age of Onset; D000818:Animals; D000831:Animals, Newborn; D019138:Antibodies, Blocking / Q000378:metabolism; D002478:Cells, Cultured; D002689:Chlamydia / Q000276:immunology*; D061387:Chlamydial Pneumonia / Q000453:epidemiology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012130:Respiratory Hypersensitivity / Q000453:epidemiology / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D050800:STAT6 Transcription Factor