COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV

Abstract

IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.

IL-20 Cytokines Are Involved in Epithelial Lesions Associated with Virus-Induced COPD Exacerbation in Mice

“…This increase in antiviral pathway, including RIG-I, Rsad-2 and IFN-λ2/3, was linked to an increased PVM detection in the lung of CS-exposed mice. This was consistent with other studies demonstrating the increased expression of antiviral elements such as MDA-5, IFN-β and IFN-λ1, by bronchial epithelial cells from COPD patient stimulated by rhinovirus or RSV [ 31 , 32 ] and leading to an increased viral burden in mice that, in turn, might be responsible for the increased anti-viral response [ 33 ]. Similarly to RSV, PVM infection enhanced inflammation associated with perivascular and bronchial damages in CS-exposed mice [ 33 ].…”

Dynamics and Viability of Airborne Respiratory Syncytial Virus under Various Indoor Air Conditions

“…Infectious RSV titers were determined by plaque formation on confluent monolayers of Hep-2 cells as previously described . The cells were cultured in Opti-MEM containing 10% (v/v) FBS and 1% antibiotic–antimycotic (15240096, Life Technologies) in tissue culture flasks and then seeded onto 24-well plates.…”

“…Infectious RSV titers were determined by plaque formation on confluent monolayers of Hep-2 cells as previously described. 28 The cells were cultured in Opti-MEM containing 10% (v/v) FBS and 1% antibiotic−antimycotic (15240096, Life Technologies) in tissue culture flasks and then seeded onto 24-well plates. Virus samples were diluted in Opti-MEM to generate 10-fold dilutions, which were used to infect duplicate wells of Hep-2 cells under a 0.8% methyl cellulose/ Opti-MEM overlay of Opti-MEM, 1% antibiotic−antimycotic, and 0.8% methyl cellulose (9004−67−5, Merck).…”

PANoptosis: Mechanism and Role in Pulmonary Diseases

“…IFNγ is known to be elevated in COPD patients, and it is reported to enhance LPS-induced STAT1 activation in AM in COPD patients [124,125]. Furthermore, in virus infection-induced COPD exacerbation, the production of IFNβ is raised, although it is known to be deficient in COPD patients [126,127]. PANoptosis may play a unique role in infection-induced COPD exacerbation [6,7,120].…”