posted on 2013-07-17, 08:46authored byMina Jasmin Fadaee-Shohada
Cilia are hair-like structures that extend from the surface of cells, including the lining of the respiratory tract and the ependymal surface of brain ventricles. Cilia have a role in host defence as the coordinated beating of cilia keeps the epithelium layer clear of debris and pathogens. Defects in the ciliary structure are associated with a wide range of human diseases, including meningitis and primary ciliary dyskinesia (PCD).
This thesis describes the effect of Listeria monocytogenes, a model pathogen that causes meningitis and encephalitis, on rat brain ependymal cilia. This interaction resulted in an altered behaviour of both ependymal cilia and listeria, but was dependent on the listeria strain used. Commonly, listeria attached to cilia and formed aggregates which reduced the ciliary beat amplitude (the distance between the maximum forward position of the cilia tip and the maximum backward position of the ciliary tip). Cilia outside the aggregates also displayed reduced ciliary beat amplitude but this was not as low as those cilia associated with aggregates. Ciliary beat frequency within the aggregates was unchanged. The formation of listerial aggregates appeared to be dependent on a transcription factor that regulates virulence (PrfA), since mutants with a PrfA deletion did not form aggregates.
Secondly, this thesis investigated the effect of Streptococcus pneumoniae on respiratory epithelium from PCD and healthy individuals. PCD is a chronic respiratory disease where cellular output of nitric oxide is very low. Pneumococcal challenge of healthy ciliated epithelium resulted in an increase in nitric oxide, which was not observed in ciliated epithelium from PCD patients. Conversely, ciliated epithelium from PCD patients displayed significantly higher levels of some cytokine and chemokines both before and after pneumococcal infection, compared to healthy ciliated epithelium. Interestingly, ciliated epithelium from PCD patients with a ciliary static phenotype displayed the highest levels of cytokine and chemokines, both at basal level and following pneumococcal infection. As with listeria, pneumococci were also shown to bind to cilia and form aggregates. This phenomenon appeared to be initiated by pneumococcal binding to the tip of the cilium. The formation of aggregates was dependent on neuraminidase A (NanA), a key virulence factor that aids adherence, since NanA mutants did not form any aggregates.