title: Adult asthmatics display exaggerated IFNgamma responses to human metapneumovirus and respiratory syncytial virus.
abstract: Human metapneumovirus and respiratory syncytial virus are RNA viruses associated with lower respiratory tract infections. Regular symptomatic re-infection and sequelae are common, particularly in individuals with pre-existing respiratory diseases, such as asthma. Our understanding of virus-dependent cytokine responses and potential differences between allergic asthmatics and non-asthmatics is limited. To test our hypothesis that adults with mild allergic asthma, the most common form of this disease, exhibit distinct pro-inflammatory responses, we developed a model using acute in vitro infection of fresh peripheral blood mononuclear cells. For both viruses, the production of innate-immunity-associated IL-6 and IL-10 was indistinguishable in the 2 populations. Type 1 cytokine production dominated adaptive immune responses in both asthmatic and non-asthmatic individuals. Surprisingly, asthmatics exhibited stronger pro-inflammatory IFNgamma production in response to human metapneumovirus than non-asthmatic adults (p = 0.01), with a similar, but statistically nonsignificant trend in the respiratory-syncytial-virus-stimulated response. Neutralizing IL-10 did not enhance the intensity of IFNgamma responses, demonstrating that this pro-inflammatory bias is not counter-regulated by IL-10. Finally, anti-TLR4 blocked lipopolysaccharide, but not respiratory-syncytial-virus-driven cytokine production. Collectively, the data demonstrate that asthma is characterized by markedly stronger pro-inflammatory IFNgamma responses to pneumoviruses than their non-asthmatic counterparts. This distinctive pattern of viral immunity may contribute to a worsening of asthma symptoms during respiratory virus infections.
authors.affiliation: CIHR National Training Program in Allergy and Asthma Research, Department of Immunology, University of Manitoba, 603 Basic Medical Sciences Building, 730 William Ave, Winnipeg, MB R3E0W3, Canada.
authors.forename: Renée N
authors.initials: RN
authors.lastname: Douville
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bastien
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: F Estelle R
authors.initials: FE
authors.lastname: Simons
authors.forename: Kent T
authors.initials: KT
authors.lastname: HayGlass
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D029121:Metapneumovirus / Q000276:immunology*; D008875:Middle Aged; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D007371:Interferon-gamma