Cilia and Mucociliary Clearance

Bustamante-Marin, Ximena M.; Ostrowski, Lawrence E.

doi:10.1101/cshperspect.a028241

Cited by 529 publications

(456 citation statements)

References 127 publications

(152 reference statements)

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“…Differentiation of the cells lasts more than a week. In this time, the epithelial cell layer is able to maintain the barrier function, but, as discussed above, the mucociliary clearance function is impaired (43). Another consequence of the regeneration process is that the cell layer has a reduced thickness.…”

Section: Discussionmentioning

confidence: 99%

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

et al. 2019

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Streptococcus suis is an important zoonotic pathogen which can infect humans and pigs worldwide, posing a potential risk to global public health. Suilysin, a pore-forming cholesterol-dependent cytolysin, is considered to play an important role in the pathogenesis of S. suis infections. It is known that infection with influenza A viruses may favor susceptibility to secondary bacterial infection, resulting in more severe disease and increased mortality. However, the molecular mechanisms underlying these coinfections are incompletely understood. Applying highly differentiated primary porcine respiratory epithelial cells grown under air-liquid interface (ALI) conditions, we analyzed the contribution of swine influenza viruses (SIV) to the virulence of S. suis, with a special focus on its cytolytic toxin, suilysin. We found that during secondary bacterial infection, suilysin of S. suis contributed to the damage of well-differentiated respiratory epithelial cells in the early stage of infection, whereas the cytotoxic effects induced by SIV became prominent at later stages of infection. Prior infection by SIV enhanced the adherence to and colonization of porcine airway epithelial cells by a wild-type (wt) S. suis strain and a suilysin-negative S. suis mutant in a sialic acid-dependent manner. A striking difference was observed with respect to bacterial invasion. After bacterial monoinfection, only the wt S. suis strain showed an invasive phenotype, whereas the mutant remained adherent. When the epithelial cells were preinfected with SIV, the suilysin-negative mutant also showed an invasion capacity. Therefore, we propose that coinfection with SIV may compensate for the lack of suilysin in the adherence and invasion process of suilysin-negative S. suis. FIG 4Invasion of the bronchiolar epithelium by S. suis after preinfection with SIV. PBEC were preinfected with 5 ϫ 10 4 TCID 50 /filter H3N2 for 24 h, subsequently inoculated with S. suis wt strain 10 or the 10Δsly mutant at 2.5 ϫ 10 7 /filter from the apical compartment for 4 h, and then washed thoroughly to remove nonadherent bacteria and further incubated under ALI conditions until 48 hpi. Before fixation, the infected cells were washed with PBS to remove nonadherent bacteria. PBEC monoinfected with S. suis wt strain 10, the 10Δsly mutant, or H3N2 and mock-infected cells served as controls. (A) Immunostaining detection for colocalization of streptococci with H3N2-infected cells in the bronchiolar epithelium. Streptococci are labeled in green, nucleoproteins of H3N2 are stained in red, and nuclei are shown in blue (DAPI). The areas in the squares in the center of the panels in the bottom row are magnified in the insets at the top left of those panels. Bars, 25 m. (B) Immunostaining detection for invasion of streptococci into the bronchiolar epithelium, with vertical sections of PBEC being shown. Streptococci are labeled in green, nucleoproteins of H3N2 are stained in red, and nuclei are shown in blue (DAPI). White arrows indicate tissue-invasive bacteria, and the dashed...

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Section: Discussionmentioning

confidence: 99%

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

et al. 2019

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“…By their continuous and coordinated beating, cilia transport mucus and entrapped pathogens and toxins out of the airways, helping to maintain the lung in a healthy state (1–3). Impaired mucociliary clearance is a feature of many airway diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia (PCD).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance

et al. 2017

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Cilia are essential to many diverse cellular processes. Although many major axonemal components have been identified and studied, how they interact to form a functional axoneme is not completely understood. To further our understanding of the protein composition of human airway cilia, we performed a semi-quantitative analysis of ciliary axonemes using label-free LC/MSE which identified over 400 proteins with high confidence. Tubulins were the most abundant proteins identified, with evidence for 20 different isoforms obtained. Twelve different isoforms of axonemal dynein heavy chain were also identified. Absolute quantification of the non-tubulin components demonstrated a greater than 75-fold range of protein abundance (RSPH9;1850 fmol vs CCDC103;24 fmol), adding another level of complexity to axonemal structure. Of the identified proteins, approximately 70% are known axonemal proteins. In addition, many previously uncharacterized proteins were identified. Unexpectedly, several of these, including ERICH3, C1orf87, and CCDC181, were present at high relative abundance in the cilia. RT-PCR analysis and immunoblotting confirmed cilia specific expression for eight uncharacterized proteins, and fluorescent microscopy demonstrated unique axonemal localizations. These studies have provided the first quantitative analysis of the ciliary proteome and have identified and characterized several previously unknown proteins as major constituents of human airway cilia.

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“…Divergence from these parameters, either due to environmental insults or disease, impairs optimal ciliary function and leads to compromised mucociliary clearance. Ciliary structure and function are highly vulnerable to damage from cigarette smoke, chronic inflammation, and pathogens (8,13). Primary ciliary dyskinesia, a disorder of mucociliary clearance, involves the absence or abnormal movement of cilia due to mutations in genes responsible for cilium biogenesis or motility (14).…”

Section: Motile Ciliamentioning

confidence: 99%

“…Several static in vitro culture models of human and rodent airway have been developed that allow analysis of mucin secretion, ciliary beating, and MCT (8,13,46,47). Although informative, a major limitation of these systems is that in vitroreconstituted mucociliary epithelia transport the secreted mucus in a continuous circular manner, and, as such, often fail to reproduce in vivo-observed directionality of MCT.…”

Section: Model Systems For Investigating Mucociliary Functionsmentioning

confidence: 99%

Mucociliary Defense: Emerging Cellular, Molecular, and Animal Models

et al. 2018

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Respiratory tissues are bombarded by billions of particles daily. If allowed to accumulate, these particles can cause injury, inflammation, or infection, and thus may significantly disrupt airflow and gas exchange. Mucociliary defense, a primary mechanism for protecting host tissues, operates through the coordinated functions of mucus and cilia that trap and eliminate inhaled materials. Mucociliary function is also required for the elimination of endogenous cells and debris. Although defense is necessarily robust, it is also tightly regulated to minimize physiologic disruption of the host. Indeed, mucociliary dysfunction contributes to the pathogenesis of many lung diseases-including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and cystic fibrosis-in which airflow limitation, inflammation, persistent tissue injury, and structural remodeling occur. Here, we highlight recent advances in cilia and mucin biology, the importance of well-controlled mucociliary interactions, and the need to better understand how these regulate innate barrier and immune defense.

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Cilia and Mucociliary Clearance

Cited by 529 publications

References 127 publications

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance

Mucociliary Defense: Emerging Cellular, Molecular, and Animal Models

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