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|Title: ||Role of the Lectin Pathway Recognition Molecule Ficolin A in Fighting Pneumococcal Infection|
|Authors: ||Haleem, Syed Kashif|
|Supervisors: ||Schwaeble, Wilhelm|
|Award Date: ||22-Jun-2012|
|Presented at: ||University of Leicester|
|Abstract: ||Complement system is an essential part of innate immune system that plays major role in protection against various pathogens, including Streptococcus pneumoniae. Complement is activated via three pathways; the classical pathway, the alternative pathway and the lectin pathway. Lectin pathway of complement activation is mediated via ficolins, MBL and recently described C-type lectin, CL-11, that recognise a wide range of carbohydrates on microbial surfaces and activate the complement system via MASP-2, the effector enzyme of the lectin pathway of complement activation. A significant role of the lectin pathway has been described previously using MASP-2 deficient mice, with a complete deficiency of the lectin activation pathway specific C3 and C5 converting enzymes C4b2a and C4b2a(3b)n respectively. However, the role of MBL, ficolins and CL-11 in activating lectin pathway against S. pneumoniae has not been fully characterised.
In vitro studies demonstrate that ficolin A and CL-11 are the relevant carbohydrate recognition molecules that can activate the lectin pathway of complement on the surface of S. pneumoniae. The protective activity of ficolin A was demonstrated in vivo using ficolin A-/- mice compared to wild-type controls, the ficolin A-/- mice were highly susceptible to pneumococcal infection with higher mortality and higher bacterial burden in both blood and lungs after intranasal infection with S. pneumoniae D39 compared to wild-type controls. These findings imply that the lectin pathway has a significant role in protection against S. pneumoniae infection and highlights the importance of non-MBL mediated lectin pathway activation in the innate host defence against S. pneumoniae.
The essential role of the lectin pathway in providing protection against S. pneumoniae was further described by blocking the lectin pathway by i.p. injection of mice with anti-MASP-2 mAb. Mice receiving anti-MASP-2 mAb showed significantly higher mortality after intranasal infection with S. pneumoniae when compared to mice receiving control antibody.|
|Rights: ||Copyright © the author, 2012|
|Appears in Collections:||Leicester Theses|
Theses, Dept. of Infection, Immunity and Inflammation
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