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The role of CL-11, a novel recognition component of the lectin activation pathway of complement in pneumococcal infection

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thesis
posted on 10.07.2017, 09:09 by Ibtihal Abdulhadi Majeed Al-karaawi
The Lectin activation Pathway of complement (LP) is initiated by LP specific recognition molecules, i.e. MBL, CL-11 and ficolins. These subcomponents recognize a wide range of carbohydrates or acetylated structures on microbial surfaces and activate complement via the LP effector enzyme MASP-2. The essential role of the LP in fighting S. pneumoniae infections was first shown by Prof. Schwaeble’s team using a mouse line deficient of MASP-2 and in mice deficient of the murine LP recognition component Ficolin A. This is the first report showing that CL- 11, an only recently identified recognition subcomponent of the LP, is critical in the innate immune defense against S. pneumoniae infections. My in vivo work was supported by numerous in vitro analyses using native and recombinant murine CL-11 revealing that this recognition subcomponent critically contributes to complement activation the surface of S. pneumoniae. So far, I compared the susceptibility of CL-11 deficient mice with that of sex, age and strain matched wildtype control mice and this analysis revealed a dramatically increased mortality in CL-11 deficient mice with a significant increase of bacteraemia in CL-11-/-mice. Another aspect of my study was to assess whether any of the SNPs described for the human CL-11 gene pre-disposes for frequent microbial infections. Also the effects of genetic variations (SNPs) in the promoter on CL-11 expression were studied using a set of nested deletions cloned into an in vitro reporter vector system.

History

Supervisor(s)

Schwaeble, Wilhelm; Wallis, Russell

Date of award

30/06/2017

Author affiliation

Department of Infection, Immunity and Inflammation

Awarding institution

University of Leicester

Qualification level

Doctoral

Qualification name

PhD

Language

en

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