Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis

Abstract

Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung.

Characterization of cellular transcriptomic signatures induced by different respiratory viruses in human reconstituted airway epithelia

“…In addition, hRSV has also been reported to induce an increase on ciliary dyskinesis combined with ciliary loss and epithelial damage, hence resulting in a strong decrease of mucociliary clearance 36 . This interplay between respiratory viruses and the cilium-related machinery is of great interest, even more in the context of pathological defective mucociliary clearance such as cystic fibrosis, where co-infections are known to be associated with more severe respiratory pathologies 37,38 .…”

Novel protective mechanism for interleukin-33 at the mucosal barrier during influenza-associated bacterial superinfection

“…In addition to gram-positive bacteria, gram-negative bacteria can also cause bacterial super-infection following influenza. Patients with chronic respiratory disease such as chronic obstructive pulmonary disease and cystic fibrosis are frequently colonized with gram-negative bacteria and viral infections such as influenza can lead to increased bacterial burden and exacerbation of disease 25 . IL-33 has been shown to polarize macrophages to an alternative activated macrophage phenotype (M2a), decrease bacterial load, and decrease neutrophil infiltrate during Pseudomonas aeruginosa keratitis 8 .…”

The Virome of the Human Respiratory Tract

“…Although many viral infections are mild or resolve without complication in generally healthy individuals, viruses in the respiratory tract are associated with exacerbations of chronic lung diseases, including CF, chronic obstructive pulmonary disease, and asthma (reviewed in the following 11,12 ). Exploration of the virome in the respiratory tracts of patients with chronic lung diseases has emphasized the prevalence of common pathogens and also further defines the scope of the respiratory tract virome.…”