The Streptococcus pneumoniae capsule is an essential virulence factor and it is ideally situated to modulate interactions between the bacteria and host immune cells. Using isogenic unencapsulated mutants, flow cytometry assays and a mouse septicaemia model, this thesis has assessed the effects of the capsule on the interactions of S. pneumoniae serotype 2 and 4 strains with complement factors and phagocytes. Overall, these data demonstrate that the capsule inhibits complement activity but this only partially contributes to the effects of the capsule on neutrophil phagocytosis and virulence during septicaemia. Furthermore, interactions with macrophages were also found to be complement-dependent and independent, resulting in differences in both phagocytosis and inflammatory responses both in vitro cell line and in vivo. I also investigated whether capsular serotype affects S. pneumoniae interactions with the host immune response using otherwise isogenic TIGR4 strains expressing capsular serotypes 4, 6A, 7F, 23F. These data demonstrate that resistance to complement mediated immunity is associated with capsular serotype, and hence this might be one mechanism by which capsular serotype could affect relative invasiveness of S. pneumoniae strains. Noncapsular genetic background was also found to affect complement mediated immunity, and importantly, relatively invasive strains were on average more resistant to complement than weakly invasive strains. Overall the results in this thesis demonstrate that the S. pneumoniae capsule aids evasion of both complement dependent and independent immune mechanisms, and that serotypedependent differences in the effects on immunity could partially explain variations in virulence between strains.
|Creators||Hyams, C. J.|
|Publisher||University College London (University of London)|
|Source Sets||Ethos UK|
|Type||Electronic Thesis or Dissertation|
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