First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Abstract

Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens, including viruses, bacteria, and fungi, have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections are still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immunoregulatory roles during infection will also be discussed.

Keywords: Aspergillus; Hemophilus influenzae; Pseudomonas aeruginosa; Streptococcus pneumoniae; chronic rhinosinusitis; coronavirus; cystic fibrosis; influenza; lung epithelium; primary ciliary dyskinesia; rhinovirus.

Fig. 1.

A: cross-section of differentiated conducting airway epithelium, consisting of ciliated columnar epithelial cells and secretory goblet cells. Apical airway surface liquid (ASL) is made up of a low-viscosity periciliary layer (PCL) that enables efficient ciliary beating, whereas an upper mucus layer functions to entrap inhaled pathogens. B: differential interference contrast (DIC) micrograph of air-liquid interface (ALI)-cultured primary nasal airway epithelial cells showing brushlike ciliated cells surrounded by secretory goblet cells. C: immunofluorescence of ALI-cultured primary nasal epithelial cells for β-tubulin IV (green), showing densely ciliated surface. Nuclei were stained with DAPI (blue). Image was taken at ×60.

Fig. 2.

A: transverse section of motile cilia illustrating the major structures of the 9 + 2 microtubule arrangement. B: the mechanical force generated by beating cilia is driven by a rapid power stroke (steps 1–5), followed by a slower recovery stroke (steps 6–8). Continual and coordinated oscillations of cilia move mucus out of the airways. AECs, airway epithelial cells.

Fig. 3.

Bacteria adhering to ciliated tissue removed from a patient with chronic rhinosinusitis. Cilia were stained with antibody for β-tubulin IV (green), and bacterial DNA was stained with DAPI (magenta). Confocal immunofluorescence slice was taken at ×60 as described previously (63).