Adult asthmatics display exaggerated IFNγ responses to human metapneumovirus and respiratory syncytial virusThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process

Autor: F. Estelle R. Simons, Nathalie Bastien, Kent T. HayGlass, Renée N. Douville, Yan LiY. Li
Rok vydání: 2007
Předmět:
Zdroj: Biochemistry and Cell Biology. 85:252-258
ISSN: 1208-6002
0829-8211
Popis: 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 IFNγ 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 IFNγ 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 IFNγ 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.
Databáze: OpenAIRE