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Interactions between Pathways of the Complement System and Neisseria meningitidis

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posted on 17.09.2018, 11:50 by Homam Helal Ageel
Neisseria meningitidis is the main cause of bacterial meningitis among adults. It can also invade the blood stream causing systematic infection sepsis, which can lead to septic shock. The most frequently isolated strain associated with disease in the UK is the genogroup B strain MC58. The complement system is known to be an important part of the immune system. There are many reports of recurrent meningococcal infections in individuals with genetic mutations causing partial or total malfunction of the complement system. Two of the pathways of complement, the Lectin (LP) and Alternative (AP) pathways are activated by recognition molecules binding to components of the bacterial surface. These recognition molecules are collectin 11 (CL-11), Ficolins and Mannan-binding Lectins (MBL), associated with MBL-associated serine proteases (MASPs), which ultimately activate either the LP and/or the AP. It is unclear, however, which recognition molecules interact with N. meningitidis. Therefore, in-vitro studies of the interaction between different complement components and different clonal complexes of N. meningitidis were undertaken, via assays of C3 and C5b-9 deposition. It was found that CL-11 is the major recognition molecule for different clonal complexes of N. meningitidis genogroup B, while MBL is the major recognition molecule for genogroup Y. It was found also that the capsule and the phase variation of MC58 have no significant impact on its recognition. In-vivo, the effect of inhibition of MASP-2 or MASP-3 on the survival of animals vaccinated against genogroup B and infected with MC58 was also studied. Vaccination overcomes the effect of inhibition of the LP or the AP in infected mice.

History

Supervisor(s)

Andrew, Peter; Lynch, Nicholas

Date of award

24/08/2018

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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