Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and T2 mediators. With the renewed interest in anti-T2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis.

The rapid recruitment of ILC2s to the upper airways of allergic patients with rhinitis, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergens in the airways. The novel methodology described herein enables the analysis of rare cell populations from noninvasive serial tissue sampling.

At a GlanceWhat is the current scientific knowledge on this subject? Enrichment of type 2 innate lymphoid cells (ILC2s) has been previously shown in patients with asthma, including in the nasal mucosa in response to allergen challenge. The potential role of ILC2s in rhinovirus-induced asthma exacerbations is not well-characterized, including the kinetics and relative contributions of different ILC subsets in response to rhinovirus infection. What does this study add to the field?This study demonstrates differential ILC1 and ILC2 responses in the lower airways of patients with asthma and healthy subjects following experimental rhinovirus challenge. An ILC2-predominant response was associated with greater severity of rhinovirus infection in asthma, as determined by greater reductions in lung function AJRCCM Articles in Press.