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Complement and surfactant Protein D in the innate immunity to streptococcus pneumoniae

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thesis
posted on 15.12.2014, 10:33 by Rania Ahmad Jounblat
The aim of this project was to investigate the role of complement and lung surfactant protein D in innate immunity to S. pneumoniae.;Pneumolysin, a cytolytic toxin produced by S. pneumoniae, is able to activate the classical complement pathway. The deletion of the ability of pneumolysin to activate complement affected the early growth of pneumococcus in the lungs, the onset of bacteraemia, the histological changes and the recruitment of T lymphocytes into lung tissue during bronchopneumonia.;Lung complement C3 was substantially activated after intranasal infection with wild-type S. pneumoniae in comparison with the isogenic mutant strain unable to produce pneumolysin (PLN-A).;Data presented in this thesis showed that the classical complement pathway plays a critical role in the innate immunity to S. pneumoniae infection. Deficiency in C1q increased the susceptibility to pneumococcal infection and was associated with defects in pneumococcal clearance from lungs and blood, less severe histological changes, recruitment of T cells and a substantial decrease in the activation of complement C3 in the lung.;In vitro studies showed that lung surfactant protein D or its receptor gp-340 is able to bind and agglutinate several strains of S. pneumoniae. Sp-D did not enhance the uptake of pneumococcus by neutrophils. The capsule-type is not a determinant for S. pneumoniae aggregation by Sp-D or gp-340.;Sp-D-deficient mice showed increased susceptibility to pneumococcal infection. Deficiency in Sp-D was associated with decreased pneumococcal clearance in lungs and trachea, early onset and increased levels of bacteraemia. In the infected lung, accumulation of T lymphocytes and more severe inflammation were observed in the absence of Sp-D.

History

Date of award

01/01/2003

Author affiliation

Microbiology

Awarding institution

University of Leicester

Qualification level

Doctoral

Qualification name

PhD

Language

en

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