Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children

Subrata, Lily S., Bizzintino, Joelene, Mamessier, Emilie, Bosco, Anthony, McKenna, Katherine L., Wikstrom, Matthew E., Goldblatt, Jack, Sly, Peter D., Hales, BelindaJ, Thomas, Wayne R., Laing, Ingrid A., LeSouef, Peter N. and Holt, Patrick G. (2009) Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children. Journal of Immunology, 183 4: 2793-2800. doi:10.4049/jimmunol.0900695


Author Subrata, Lily S.
Bizzintino, Joelene
Mamessier, Emilie
Bosco, Anthony
McKenna, Katherine L.
Wikstrom, Matthew E.
Goldblatt, Jack
Sly, Peter D.
Hales, BelindaJ
Thomas, Wayne R.
Laing, Ingrid A.
LeSouef, Peter N.
Holt, Patrick G.
Title Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2009-08-01
Sub-type Article (original research)
DOI 10.4049/jimmunol.0900695
Volume 183
Issue 4
Start page 2793
End page 2800
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Abstract Severe asthma exacerbations in children requiring hospitalization are typically associated with viral infection and occur almost exclusively among atopics, but the significance of these comorbidities is unknown. We hypothesized that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during exacerbation vs convalescence by microarray and flow cytometry. We demonstrate that circulating T cells manifest the postactivated "exhausted" phenotype during exacerbations, whereas monocyte/dendritic cell populations display up-regulated CCR2 expression accompanied by phenotypic changes that have strong potential for enhancing local inflammation after their recruitment to the atopic lung. Notably, up-regulation of FcεR1, which is known to markedly amplify capacity for allergen uptake/presentation to Th2 effector cells via IgE-mediated allergen capture, and secondarily programming of IL-4/IL-13-dependent IL-13R+ alternatively activated macrophages that have been demonstrated in experimental settings to be a potent source of autocrine IL-13 production. We additionally show that this disease-associated activation profile can be reproduced in vitro by cytokine exposure of atopic monocytes, and furthermore that IFN-αcan exert both positive and negative roles in the process. Our findings suggest that respiratory viral infection in atopic children may initiate an atopy-dependent cascade that amplifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing underlying atopy-associated mechanisms. These interactions may account for the unique susceptibility of atopics to severe viralinduced asthma exacerbations.
Keyword Fc-epsilon-ri
Allergic airway inflammation
Killer T-cells
Dendritic Cells
Respiratory-tract
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Health and Behavioural Sciences -- Publications
 
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Created: Wed, 17 Nov 2010, 21:53:00 EST