Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice

Kaiko, Gerard E., Loh, Zhixuan, Spann, Kirsten, Lynch, Jason P., Lalwani, Amit, Zheng, Zhenglong, Davidson, Sophia, Uematsu, Satoshi, Akira, Shizuo, Hayball, John, Diener, Kerrilyn R., Baines, Katherine J., Simpson, Jodie L., Foster, Paul S. and Phipps, Simon (2013) Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice. Journal of Allergy and Clinical Immunology, 131 5: 1331-133e10. doi:10.1016/j.jaci.2013.02.041


Author Kaiko, Gerard E.
Loh, Zhixuan
Spann, Kirsten
Lynch, Jason P.
Lalwani, Amit
Zheng, Zhenglong
Davidson, Sophia
Uematsu, Satoshi
Akira, Shizuo
Hayball, John
Diener, Kerrilyn R.
Baines, Katherine J.
Simpson, Jodie L.
Foster, Paul S.
Phipps, Simon
Title Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice
Journal name Journal of Allergy and Clinical Immunology   Check publisher's open access policy
ISSN 0091-6749
1097-6825
Publication date 2013-05-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.jaci.2013.02.041
Open Access Status Not yet assessed
Volume 131
Issue 5
Start page 1331
End page 133e10
Total pages 19
Place of publication Philadelphia, PA United States
Publisher Mosby
Language eng
Subject 2723 Immunology and Allergy
2403 Immunology
Abstract Background: Respiratory tract viruses are a major environmental risk factor for both the inception and exacerbations of asthma. Genetic defects in Toll-like receptor (TLR) 7-mediated signaling, impaired type I interferon responses, or both have been reported in asthmatic patients, although their contribution to the onset and exacerbation of asthma remains poorly understood. Objective: We sought to determine whether Pneumovirus infection in the absence of TLR7 predisposes to bronchiolitis and the inception of asthma. Methods: Wild-type and TLR7-deficient (TLR7) mice were inoculated with the rodent-specific pathogen pneumonia virus of mice at 1 (primary), 7 (secondary), and 13 (tertiary) weeks of age, and pathologic features of bronchiolitis or asthma were assessed. In some experiments infected mice were exposed to low-dose cockroach antigen. Results: TLR7 deficiency increased viral load in the airway epithelium, which became sloughed and necrotic, and promoted an IFN-α/β, IL-12p70, IL- 1β, IL-25, and IL-33 cytokine microenvironment that was associated with the recruitment of type 2 innate lymphoid cells/nuocytes and increased T2-type cytokine production. Viral challenge of TLR7 mice induced all of the cardinal pathophysiologic features of asthma, including tissue eosinophilia, mast cell hyperplasia, IgE production, airway smooth muscle alterations, and airways hyperreactivity in a memory CD4 T cell-dependent manner. Importantly, infections with pneumonia virus of mice promoted allergic sensitization to inhaled cockroach antigen in the absence but not the presence of TLR7. Conclusion: TLR7 gene defects and Pneumovirus infection interact to establish an aberrant adaptive response that might underlie virus-induced asthma exacerbations in later life.
Keyword Toll like receptor 7
Pneumovirus
Infection
Type 2 innate lymphoid cell
Nuocyte
Asthma
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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