title: RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma.
abstract: Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target.
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Jaisy
authors.initials: J
authors.lastname: Arikkatt
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.|Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, New South Wales, Australia.
authors.forename: Md Ashik
authors.initials: MA
authors.lastname: Ullah
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.|Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Kirsty Renfree
authors.initials: KR
authors.lastname: Short
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Vivan
authors.initials: V
authors.lastname: Zhang
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Wan Jun
authors.initials: WJ
authors.lastname: Gan
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Zhixuan
authors.initials: Z
authors.lastname: Loh
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Rhiannon B
authors.initials: RB
authors.lastname: Werder
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Simpson
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|Centre for Children's Health Research Children's Health Queensland, The University of Queensland, Brisbane, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Mazzone
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Australia.|School of Biomedical Science, Queensland University of Technology, Brisbane, Australia.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Spann
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Manuel Ar
authors.initials: MA
authors.lastname: Ferreira
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|School of Medicine, The University of Queensland, Princess Alexandra Hospital Brisbane, Brisbane, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.affiliation: Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, New South Wales, Australia.|Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, Australia.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Sukkar
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, Australia.|Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Simon
authors.identifier: 0000-0002-7388-3612
authors.initials: S
authors.lastname: Phipps
mesh_terms: D000380:Agranulocytosis / Q000150:complications* / Q000235:genetics*; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D024243:HMGB1 Protein / Q000378:metabolism*; D051379:Mice; D029122:Murine pneumonia virus / Q000276:immunology; D000067759:Receptor for Advanced Glycation End Products / Q000172:deficiency*; D019562:Viral Load
chemical_list: C000593873:Ager protein, mouse; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D000067759:Receptor for Advanced Glycation End Products
keywords: HMGB1; RAGE; asthma; immunology; infectious disease; microbiology; mouse; paucigranulocytic; virus infection