Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity

Abstract

Background: Viral infections, especially those caused by rhinovirus, are the most common cause of asthma exacerbations. Previous studies have argued that impaired innate antiviral immunity and, as a consequence, more severe infections contribute to these exacerbations.

Objective: These studies explored the innate immune response in the upper airway of volunteers with allergic rhinitis and asthma in comparison to healthy controls and interrogated how these differences corresponded to severity of infection.

Methods: Volunteers with allergic rhinitis, those with asthma, and those who are healthy were inoculated with rhinovirus A16 and monitored for clinical symptoms. Tissue and nasal wash samples were evaluated for antiviral signature and viral load.

Results: Both subjects with allergic rhinitis and asthma were found to have more severe cold symptoms. Subjects with asthma had worsened asthma control and increased bronchial hyperreactivity in the setting of higher fractional exhaled breath nitric oxide and blood eosinophils. These studies confirmed reduced expression of interferons and virus-specific pattern recognition receptors in both cohorts with atopy. Nevertheless, despite this defect in innate immunity, volunteers with allergic rhinitis/asthma had reduced rhinovirus concentrations in comparison to the controls.

Conclusion: These results confirm that the presence of an allergic inflammatory disorder of the airway is associated with reduced innate immune responsive to rhinovirus infection. Despite this, these volunteers with allergy have reduced viral loads, arguing for the presence of a compensatory mechanism to clear the infection.

Trial registration: ClinicalTrials.gov Identifier: NCT02910401.

Conflict of interest statement

Conflict of interest: None of the authors report any conflict of interest relevant to the current submission.

Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1:

Clinical response to RV infection. 1A. Upper respiratory symptoms in control (C), AR, and asthmatics (A) post-viral inoculation. 1B. FEV1/FVC ratio. 1C. Circulating absolute eosinophil count. 1D. FeNO. *p§p<0.01 compared to day 0; †p<0.05 compared to day 0.

Figure 2:

Immunofluorescence staining of eosinophil-derived EDN and MBP at dpi 4. 2A. Representative staining. 2B: Summary of expression of EDN. **p#p<0.05 atopic subjects day 4 compared to day 0.

Figure 3

qPCR for RV sensing and responding molecules: 3A – IFN-α, 3B – IFN-ß, 3C – IFN-λ, 3D – RIG-I, 3E – TLR3, 3F – MDA5. Vertical bars on the right of each graph indicate significant difference between the two groups. and the * above, indicate the specific day these differences were significant. *p

Figure 4:

Immunofluorescent staining of RV-sensing and anti-viral responding molecules. 4A. Representative immunofluorescent staining. Images are shown at 200x with digital enlargement of key areas (dotted lines) to enhance visibility of details (inset, solid lines). 4B. Expression of RV-sensing and anti-viral responding molecules via IF. Statistical analyses involved unpaired t-tests. *p

Figure 4:

Immunofluorescent staining of RV-sensing and anti-viral responding molecules. 4A. Representative immunofluorescent staining. Images are shown at 200x with digital enlargement of key areas (dotted lines) to enhance visibility of details (inset, solid lines). 4B. Expression of RV-sensing and anti-viral responding molecules via IF. Statistical analyses involved unpaired t-tests. *p

Figure 5:

Rhinovirus expression post-inoculation. 5A. Representative RV immunofluorescence staining showing viral protein in submucosal (but not epithelial) tissue. 5B. Summary of IF of RV positive cells at dpi 4. *p

Figure 6

Model for the development of asthma exacerbations in response to RV infections. See text for details.