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

J Allergy Clin Immunol. 2013 May;131(5):1331-9.e10. doi: 10.1016/j.jaci.2013.02.041. Epub 2013 Apr 2.


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(low), IL-12p70(low), IL-1β(high), IL-25(high), and IL-33(high) cytokine microenvironment that was associated with the recruitment of type 2 innate lymphoid cells/nuocytes and increased TH2-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Asthma / etiology
  • Asthma / immunology*
  • Asthma / pathology*
  • Disease Models, Animal
  • Lung / pathology
  • Lung / physiopathology
  • Lung / virology
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Murine pneumonia virus* / pathogenicity
  • Pneumovirus Infections / complications*
  • Pneumovirus Infections / immunology
  • Pneumovirus Infections / pathology
  • Toll-Like Receptor 7 / deficiency*
  • Toll-Like Receptor 7 / genetics*
  • Viral Load


  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7