Viral Infection and Airway Epithelial Immunity in Asthma

Abstract

Viral respiratory tract infections are associated with asthma development and exacerbation in children and adults. In the course of immune responses to viruses, airway epithelial cells are the initial platform of innate immunity against viral invasion. Patients with severe asthma are more vulnerable than those with mild to moderate asthma to viral infections. Furthermore, in most cases, asthmatic patients tend to produce lower levels of antiviral cytokines than healthy subjects, such as interferons produced from immune effector cells and airway epithelial cells. The epithelial inflammasome appears to contribute to asthma exacerbation through overactivation, leading to self-damage, despite its naturally protective role against infectious pathogens. Given the mixed and complex immune responses in viral-infection-induced asthma exacerbation, this review examines the diverse roles of airway epithelial immunity and related potential therapeutic targets and discusses the mechanisms underlying the heterogeneous manifestations of asthma exacerbations.

The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma

“…Viral infection of the airways also has profound effects on epithelial barrier function [ 42 ]. Facilitated by a disrupted barrier, viral infection activates epithelial cells, triggering innate immune and T2 inflammatory responses, and amplifying the overall inflammation commonly present in asthma [ 42 – 44 ].…”

“…Viral infection of the airways also has profound effects on epithelial barrier function [ 42 ]. Facilitated by a disrupted barrier, viral infection activates epithelial cells, triggering innate immune and T2 inflammatory responses, and amplifying the overall inflammation commonly present in asthma [ 42 – 44 ]. However, the immune response to viral infection appears to be deficient and delayed in people with asthma, with reduced production of type I IFN and other cytokines in epithelial and dendritic cells leading to greater damage to the airway epithelium [ 45 – 47 ].…”

Progress in diagnosis and treatment of difficult-to-treat asthma in children

“…Among respiratory viruses, rhinovirus is the most important and common virus that exacerbates asthma. 50 Asthma patients may have deteriorating asthma symptoms as a result of the functional interplay between viral pathology and asthma pathology. 51 Recurrent asthma inflammation may hinder the body’s ability to mount an efficient antiviral defense, worsening the virus’s already-present airway destruction.…”

Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases

“…Studies have shown that opening the epithelial barrier induces inflammatory responses and increased epithelial permeability, creating a vicious cycle that potentiates dysregulated subepithelial immune responses and more exposure to allergens and irritants. 70 132 Cell-cell adhesion complexes (TJ, AJ, desmosome) are the key regulators of paracellular permeability. 133 TJs defects and increased epithelial permeability are the main characteristics of chronic airway disease and leaky gut syndrome.…”