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Title: Bacterial factors affecting the inflammatory response to Streptococcus pneumoniae
Author: Periselneris, J. N.
ISNI:       0000 0004 8498 8051
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Streptococcus pneumoniae is an important bacterial pathogen causing significant morbidity and mortality. The host inflammatory response to S. pneumoniae plays a critical role in escalating the host defence response to deal with large bacterial numbers, however excess inflammation can cause bystander damage. Macrophages are a key immune cell that mediates recognition of pathogens and initiates inflammatory responses. The polysaccharide capsule and toxin pneumolysin are important virulence factors that affect multiple components of the immune system. The S. pneumoniae capsule increases inflammatory responses in vitro tissue culture models, with macrophages providing the main response. This was not dependent on TLR2 signalling, phagocytosis, lectin signalling, or scavenger receptor function. Mouse pneumonia and rat septic shock modelling showed that this had in vivo correlates. This data was extended by examining the extent capsule affects inflammatory responses by using other bacteria expressing serotype 4 capsule, and serotype 4 expressing other serotypes' capsules. Pneumolysin decreases inflammatory responses in vitro, this was found to be dependent on phagocytosis and partially by its pore forming ability. This was reflected by the TNF response in mouse bronchoalveolar lavage fluid in a mouse model. Blockade of TNF abrogated differences between wild-type bacteria and pneumolysin deficient mutants. TNF administration to mice increased the ability of bronchoalveolar lavage fluid to restrict the growth of S. pneumoniae. In conclusion, capsule and pneumolysin have opposing roles in their effect on the inflammatory response. The inflammation promoting effects of capsule impact on virulence, and may increase morbidity during infection. The inflammation dampening effects of pneumolysin may be an important immune evasion strategy that explains its evolutionary conservation in S. pneumoniae.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available