Mucociliary Respiratory Epithelium Integrity in Molecular Defense and Susceptibility to Pulmonary Viral Infections

Simple Summary Mucociliary clearance constitutes an innate lung defense mechanism that is primarily driven by ciliated cells. Respiratory mucus traps pathogens entering the airways, and lung cilia propel them outward via their coordinated directional motion. Thus, damage to the component(s) of this apparatus will hamper its smooth functioning. Here, we update the cellular and molecular machinery that constitutes and regulates mucociliary clearance (MCC). We also describe several respiratory diseases arising due to genetic or acquired molecular shortcomings in the MCC. The past few decades have seen the emergence of novel viruses that inflame and damage the respiratory tract. Coronaviruses have been observed to disrupt the ciliated epithelium and abolish its integrity. Bearing in mind the havoc created by the ongoing pandemic, we outline the significance of the ciliated respiratory epithelium in defense against such microbial infections. We have predicted protein interaction networks depicting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-manifested implications on the molecular machinery regulating mucociliary clearance. Several proteins involved in the network were found to interact with SARS-CoV-2 viral proteins upon host infection. This review also emphasizes the importance of the proper management and surveillance of respiratory health in the elderly and patients with chronic respiratory diseases so that they do not bear the impact of a severe or lethal infection. Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fitness. The concerted action of ciliary movement on the respiratory epithelial surface and the pathogen entrapment function of mucus help to maintain healthy airways. Consequently, genetic or acquired defects in lung defense elicit respiratory diseases and secondary microbial infections that inflict damage on pulmonary function and may even be fatal. Individuals living with chronic and acute respiratory diseases are more susceptible to develop severe coronavirus disease-19 (COVID-19) illness and hence should be proficiently managed. In light of the prevailing pandemic, we review the current understanding of the respiratory system and its molecular components with a major focus on the pathophysiology arising due to collapsed respiratory epithelium integrity such as abnormal ciliary movement, cilia loss and dysfunction, ciliated cell destruction, and changes in mucus rheology. The review includes protein interaction networks of coronavirus infection-manifested implications on the molecular machinery that regulates mucociliary clearance. We also provide an insight into the alteration of the transcriptional networks of genes in the nasopharynx associated with the mucociliary clearance apparatus in humans upon infection by severe acute respiratory syndrome coronavirus-2.