Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

Abstract

Rationale : Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease. Objectives: We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection. Methods : Primary human airway epithelial cells grown at air-liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (R T ) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting. Measurements and Main Results : Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV-but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in R T without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease R T , suggesting a requirement for viral replication. Reduced R T was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-a, IFN-g and IL-1b reversed corresponding cytokine-induced reductions in R T but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo. Conclusions: RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function.

Hypoxia Increases Epithelial Permeability in Human Nasal Epithelia

“…23 In the human nasal mucosa, the virus infection causes the loss of ZO-1 from tight junction complexes, and the loss leads to intranasal bacterial inoculation in mice. 24 In our study, the mRNA and protein expression levels of ZO-1 and E-cadherin were decreased in hypoxia-stimulated NHNE cells. This is the first study to reveal a relationship between hypoxia and barrier dysfunction in upper airway epithelial cells by analyzing the expressions of ZO-1 and E-cadherin in the normal and hypoxic human nasal mucosa.…”

Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection

“…tract, but once colonization is established, NTHi can become pathogenic itself, or contribute to the pathology of other bacteria (10) or of viral infections that lead to increased bacterial biomass (54). It can also disrupt epithelial tight junctions, which allows bacterial invasion (55). It is possible that steroid-suppression of MAIT cells could also contribute to this initial colonization step in COPD and other airway diseases.…”

Viral–bacterial interactions in the respiratory tract

“…Sajjan et al (2008) showed that infection of polarized airway epithelial cells with HRV can lead to redistribution of the tight junction protein zona occludens 1 (ZO-1) from the membrane to the cytoplasm. Furthermore, HRV was shown to impair the repolarization of airway epithelium regenerating after injury (Faris et al, 2016).…”