Why This Matters:
- Rhinoviruses are common: Rhinovirus (RV) infection is one of the most frequent viral infections in humans, causing approximately half of all common colds. RVs can also trigger exacerbations of COPD and asthma. Numerous host factors play a key role in determining illness severity.
- Innate immune responses determine disease severity: How epithelial cells engage rhinovirus upon infection influences whether the virus is controlled early or whether excessive inflammation and symptoms are triggered.
- Interferon pathways are protective: Rapid induction of interferons in infected nasal epithelial cells creates an antiviral state that limits replication and attracts protective T cells.
- Alternate signaling promotes pathology: Engagement of pro-inflammatory pathways (e.g., NF-κB, NLRP1/IL-1 axis) drive inflammation marked by innate immune cell recruitment and mucus hyper-secretion, exacerbating airway obstruction and contributing to respiratory symptoms.
Key Findings: The authors characterized how rhinovirus engages innate immune pathways in airway epithelial cells to produce distinct host responses, using an organotypic model of the human nasal mucosa and a drug that blocked antiviral interferon responses.1
- Critical role of interferons: A rapid and robust epithelial interferon (IFN) response limits rhinovirus replication even in the absence of immune cells, underscoring the capacity of epithelial innate immunity to control infection.
- Alternative innate signaling triggers inflammation: Pharmacologic blockade of IFN singaling led to significantly higher viral replication and increased NF κB- and NLRP1- mediated inflammatory signaling, implying that that epigenitic and genetic perturbations in the IFN response might similarly drive inflammation associated with more severe symptoms.
- Variability in host responses: These differential signaling outcomes suggest that the magnitude and timing of innate responses at the level of the respiratory epithelium, not just viral load, appear to shape clinical outomes, ranging from mild cold to more severe respiratory distress.
- Barrier without immune cells: Innate defenses downstream of NF κB and NLRP1 operate within the epithelium itself, highlighting that tissue-intrinsic responses are pivotal in early infection.
- Therapeutic potential: Targeting NLRP1–IL-1R- driven inflammation is a potential therapeutic strategy for mitigating rhinovirus-associated illness.
Bigger Picture: This study reinforces a core principle of respiratory virology: host innate immune engagement — particularly interferon pathways — is a key determinant of infection outcome.
Rhinoviruses are the most common cause of upper respiratory infections, yet individuals with impaired interferon responses — such as patients with asthma, COPD, or certain genetic susceptibilities — may experience more severe disease due to inadequate early antiviral signalling. In these instances, alternate innate pathways may drive excessive inflammation, mucus hypersecretion, and airway obstruction, especially in predisposed hosts.
These findings extend beyond rhinovirus. Other respiratory viruses, including SARS-CoV-2, influenza, and RSV, rely on similar epithelial interferon responses for early control. Dysregulation of these pathways may underlie variable disease severity across individuals and could inform improved therapeutic strategies.
(Image Credit: iStock/ Rasi Bhadramani)
