A human airway model for Mycoplasma pneumoniae colonization
Prince, Oliver Arnold
MetadataShow full item record
Mycoplasma pneumoniae is an important cause of acute and chronic respiratory disease, especially in school-aged children and young adults. To date, a suitable in vitro human model system for studying native mycoplasma interactions with the mucociliary defense has not been available nor has this aspect of infection been studied in detail. The current study employed normal human bronchial epithelial (NHBE) cells in air-liquid interface culture to examine the interaction(s) of M. pneumoniae with the mucociliary defense of differentiated airway epithelium. NHBE cells, when grown in air-liquid interface culture, form a pseudostratified, polarized epithelium, with tight junctions, mucus secretion, and ciliary function. The stepwise analysis of NHBE cell development and mycoplasma interactions are characterized utilizing immunohistochemistry and standard attachment assays. I have developed a model for acute and chronic exposure of M. pneumoniae to NHBE cells that details not only early localization events on the luminal surface but also mycoplasma transmigration of the paracellular surfaces and localization within the basolateral compartment, revealing a strong relationship between mycoplasma migration, desquamation and reorganization of the epithelium. This study is the first and only report to describe a link between gliding mycoplasmas, early localization, and migration through basolateral surfaces followed by loss of ciliation, desquamation and subsequent reorganization of the epithelium. These findings are essential steps in elucidating M. pneumoniae pathogenesis, in that mycoplasmas primarily localize to the basolateral surfaces where they alter mucociliary clearance via initiation of airway reorganization, a hallmark of M. pneumoniae disease in vivo, potentially reflecting a mechanism for extrapulmonary spread.