Abstract
Simple SummaryMucociliary 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.
Highlights
Life depends on the availability of oxygen in humans
The periciliary layer (PCL) volume is critical for effective Mucociliary clearance (MCC), as insufficient hydration causes the collapse of the mucus layer and the entrapment of cilia within the mucus, as seen in the case of cystic fibrosis [40]
The constructed network consists of 39 nodes that belong to different clusters representing proteins associated with the relevant processes of mucociliary clearance system, i.e., ciliogenesis, intraflagellar transport (IFT) machinery, mucins and MCC regulation, ciliary functions, and cell cycle regulation (Figure 2)
Summary
Life depends on the availability of oxygen in humans. The human respiratory system is an intricate interface for breathing and gaseous exchange. The air is filtered, warmed, and humidified during inhalation before traversing the trachea and the dichotomous respiratory airways This air stream comes close, within one cell layer barrier, to the blood stream and thereby exposes the body, via the respiratory tract, to a myriad of foreign agents like pathogenic bacteria, viruses, gaseous, and particulate matter present in the inhaled air. Mucociliary clearance (MCC) is the innate lung defense machinery used to capture and clear inhaled foreign agents [1,2]. The current situation poses an enormous challenge for managing the pulmonary diseases with an unprecedented dimension In this context, we review the important components of the human respiratory system with a specific focus on the MCC apparatus, highlighting the critical role of cilia and mucus to effectively clear pathogenic agents entering the lungs. We present an insight into the impact of SARSCoV-2 infection on molecules (proteins) associated with or involved in the mucociliary clearance system of the host
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