Adult asthmatics display exaggerated IFNgamma responses to human metapneumovirus and respiratory syncytial virus.
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.
Douville
Renée N
RN
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.
Bastien
Nathalie
N
Li
Yan
Y
Simons
F Estelle R
FE
HayGlass
Kent T
KT
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
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