Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/9969
Title: Role of the lectin pathway of complement in C. albicans and P. aeruginosa infections
Authors: Kenawy, Hany Ibrahim Mohamed
Supervisors: Schwaeble, Wilhelm
Rajakumar, Kumar
Award date: 7-Jul-2010
Presented at: University of Leicester
Abstract: Role of the lectin pathway (LP) of complement in fighting two opportunistic pathogens, Candida albicans and Pseudomonas aeruginosa was assessed through a combination of in vitro assays supported by in vivo infection experiments using a unique mouse strain of total LP functional deficiency (MASP-2 -/- mouse). A highly significant difference in survival between MASP-2 -/- mice and MASP-2 +/+ littermates was observed following C. albicans infection with a lethal i.v. dose (1.4x106CFU/mouse), showing that MASP-2 -/- were significantly compromised. Challenging mice with a sub-lethal dose (4x105 CFU/mouse) revealed a significantly higher fungal load in kidneys, livers, lungs and spleens of MASP-2 -/- mice. IL-10 mRNA expression levels were only significantly upregulated in infected MASP-2 -/- mice, while mRNA expression of the protective cytokines IL-17 and INF-γ were only upregulated in MASP-2 +/+ mice. Challenging of MASP-2 -/- mice and MASP-2 +/+ controls with an intranasal dose (1x106 CFU/mouse) of P. aeruginosa revealed no significant difference in survival rates. The bacterial load with P. aeruginosa and mRNA expression profiles for TNF-α, IL-6, IL-10, MIP-2, IL-1β and INF-γ were similar in lungs of both mouse strains. The absence of the LP in MASP-2 -/- mice appears to make no difference in the susceptibility to P. aeruginosa infection as the alternative pathway seems to provide sufficient protection. The cDNA sequence of porcine MASP-2 was established to express an enzymatically inactive mutant form of porcine MASP-2 (pMASP-2A) in a mammalian cell line (CHOK1 cells). pMASP-2A was produced in large scale and used as an antigen to isolate recombinant inhibitory phage display antibodies. These antibodies will be analysed in porcine models of ischaemia/reperfusion (I/R) injury to assess the therapeutic potential of LP inhibition in limiting I/R injury and reduce morbidity and mortality in a clinically relevant experimental animal model of human disease.
Links: http://hdl.handle.net/2381/9969
Type: Thesis
Level: Doctoral
Qualification: PhD
Sponsors / Funders: Egyptian Government
Rights: Copyright © the author, 2010.
Appears in Collections:Theses, Dept. of Infection, Immunity and Inflammation
Leicester Theses

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