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Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection.
PLoS One. 2013; 8(3):e59925.Plos

Abstract

Mucociliary airway clearance is an innate defense mechanism that protects the lung from harmful effects of inhaled pathogens. In order to escape mechanical clearance, airway pathogens including Streptococcus pneumoniae (pneumococcus) are thought to inactivate mucociliary clearance by mechanisms such as slowing of ciliary beating and lytic damage of epithelial cells. Pore-forming toxins like pneumolysin, may be instrumental in these processes. In a murine in vitro airway infection model using tracheal epithelial cells grown in air-liquid interface cultures, we investigated the functional consequences on the ciliated respiratory epithelium when the first contact with pneumococci is established. High-speed video microscopy and live-cell imaging showed that the apical infection with both wildtype and pneumolysin-deficient pneumococci caused insufficient fluid flow along the epithelial surface and loss of efficient clearance, whereas ciliary beat frequency remained within the normal range. Three-dimensional confocal microscopy demonstrated that pneumococci caused specific morphologic aberrations of two key elements in the F-actin cytoskeleton: the junctional F-actin at the apical cortex of the lateral cell borders and the apical F-actin, localized within the planes of the apical cell sides at the ciliary bases. The lesions affected the columnar shape of the polarized respiratory epithelial cells. In addition, the planar architecture of the entire ciliated respiratory epithelium was irregularly distorted. Our observations indicate that the mechanical supports essential for both effective cilia strokes and stability of the epithelial barrier were weakened. We provide a new model, where--in pneumococcal infection--persistent ciliary beating generates turbulent fluid flow at non-planar distorted epithelial surface areas, which enables pneumococci to resist mechanical cilia-mediated clearance.

Authors+Show Affiliations

Centre of Chronic Immunodeficiency, University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany. manfred.fliegauf@uniklinik-freiburg.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23527286

Citation

Fliegauf, Manfred, et al. "Mucociliary Clearance Defects in a Murine in Vitro Model of Pneumococcal Airway Infection." PloS One, vol. 8, no. 3, 2013, pp. e59925.
Fliegauf M, Sonnen AF, Kremer B, et al. Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection. PLoS One. 2013;8(3):e59925.
Fliegauf, M., Sonnen, A. F., Kremer, B., & Henneke, P. (2013). Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection. PloS One, 8(3), e59925. https://doi.org/10.1371/journal.pone.0059925
Fliegauf M, et al. Mucociliary Clearance Defects in a Murine in Vitro Model of Pneumococcal Airway Infection. PLoS One. 2013;8(3):e59925. PubMed PMID: 23527286.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection. AU - Fliegauf,Manfred, AU - Sonnen,Andreas F-P, AU - Kremer,Bernhard, AU - Henneke,Philipp, Y1 - 2013/03/19/ PY - 2012/12/13/received PY - 2013/02/19/accepted PY - 2013/3/26/entrez PY - 2013/3/26/pubmed PY - 2013/9/18/medline SP - e59925 EP - e59925 JF - PloS one JO - PLoS One VL - 8 IS - 3 N2 - Mucociliary airway clearance is an innate defense mechanism that protects the lung from harmful effects of inhaled pathogens. In order to escape mechanical clearance, airway pathogens including Streptococcus pneumoniae (pneumococcus) are thought to inactivate mucociliary clearance by mechanisms such as slowing of ciliary beating and lytic damage of epithelial cells. Pore-forming toxins like pneumolysin, may be instrumental in these processes. In a murine in vitro airway infection model using tracheal epithelial cells grown in air-liquid interface cultures, we investigated the functional consequences on the ciliated respiratory epithelium when the first contact with pneumococci is established. High-speed video microscopy and live-cell imaging showed that the apical infection with both wildtype and pneumolysin-deficient pneumococci caused insufficient fluid flow along the epithelial surface and loss of efficient clearance, whereas ciliary beat frequency remained within the normal range. Three-dimensional confocal microscopy demonstrated that pneumococci caused specific morphologic aberrations of two key elements in the F-actin cytoskeleton: the junctional F-actin at the apical cortex of the lateral cell borders and the apical F-actin, localized within the planes of the apical cell sides at the ciliary bases. The lesions affected the columnar shape of the polarized respiratory epithelial cells. In addition, the planar architecture of the entire ciliated respiratory epithelium was irregularly distorted. Our observations indicate that the mechanical supports essential for both effective cilia strokes and stability of the epithelial barrier were weakened. We provide a new model, where--in pneumococcal infection--persistent ciliary beating generates turbulent fluid flow at non-planar distorted epithelial surface areas, which enables pneumococci to resist mechanical cilia-mediated clearance. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23527286/Mucociliary_clearance_defects_in_a_murine_in_vitro_model_of_pneumococcal_airway_infection_ L2 - https://dx.plos.org/10.1371/journal.pone.0059925 DB - PRIME DP - Unbound Medicine ER -