1.1.1 Laboratory evidence linking allergy to increased risk of epithelial cells viral infection.
All experimental studies included in the qualitative analyses suggest that allergy may increase the risk of viral infections of upper airways epithelial cells consequent to Th2-polarization (Table I). The mechanisms involved may be related to enhanced adherence of pathogens to inflamed respiratory epithelium, increased mucosal permeability, altered immune response to certain viral pathogens, and excessive mucus production and modifications of mucus consistency as pabulum for microbe overgrowth(10).
Allergy may induce inflammation of the nasal mucosa leading toimpairment of epithelial barrier function and secondary deficiency of early local immune reaction. Several studies demonstrated, in fact, that the upper airway epithelium represents not only a mechanical wall against pathogens by muco-ciliary clearance, but also an immunological barrier modulating the innate immune response through cytokine production(11).
Interestingly, authors(12,13) demonstrated impairment of the overall mechanical function of the epithelium and, in particular, decreased expression of tight-junction proteins occludin and zonula occludens-1 in cultured epithelial nasal cells from allergic patients. Steelant et al.(14) demonstrated that nasal secretions from allergic subjects rapidly decrease the trans-tissue resistance of epithelial cell cultures in vitro. They also showed that anti-IL-4 treatment in mice prevented epithelial barrier disruption. Finally, several authors have demonstrated(15,16) that allergy may expedite viral overcome of mechanical barriers because TH-2 polarized cytokines such as IL-4, IL-5, and IL-13 can upregulate endothelial and epithelial expression of adhesion molecules like intercellular adhesion molecule-1 (ICAM-1), which is the receptor for 90% of rhinoviruses.
On the other hand, several authors demonstrated that allergy may modify the immunological functions of the epithelia. Many studies showed the deficiency of the innate immune response in allergic mucosa of upper and lower respiratory epithelia cells. Furthermore, it has been demonstrated in the lab that interferon production may be defective in allergic patients. Interferons are crucial for induction of apoptosis in virus-infected host cells because they prevent establishment of viral replication and promote phagocytosis of infected cells(17,18,19). Accordingly, in 2015 Teach et al.(20) found that peripheral blood mononuclear cells cultured from a subset of atopic children treated with anti-IgE improved INF-α production after incubation with rhinovirus.