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.