Bacteria-macrophage interactions in the pathogenesis of Crohn's disease

Flanagan, Paul Kevin (2017) Bacteria-macrophage interactions in the pathogenesis of Crohn's disease Doctor of Medicine thesis, University of Liverpool.

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Abstract

Crohn's disease (CD) is associated with defective innate immunity, including impaired neutrophil chemotaxis, and mucosal invasion by bacteria, particularly E. coli that replicate inside macrophage phagolysosomes. In this thesis several hypotheses were tested: (i) that CD macrophages might be defective at killing and or responding to Gram-negative bacteria, particularly E. coli; (ii) that killing of phagocytosed bacteria within macrophages might be enhanced by drugs such as hydroxychloroquine (HCQ) (previously shown to raise intravacuolar pH), and vitamin D (previously shown to enhance macrophage function). I assessed CD peripheral blood monocyte-derived macrophages (MDM) for their abilities to kill E. coli, with and without HCQ and vitamin D, and to generate neutrophil chemoattractants. MDM from patients with CD were similar to those from healthy controls (HC) in allowing replication of phagocytosed CD-derived E. coli: HM605 [CD N=10, mean fold replication in 3h: 1.08, (95% confidence interval (CI) 0.39-1.78); HC N=9, 1.50, (95%CI 1.02-1.97); P=0.15] and also in generation of neutrophil chemoattractants in response to E. coli (mean fold chemotaxis relative to control: CD 2.55, 95%CI 2.31-2.80; HC 2.65, 95%CI ... (continues)

Item Type:	Thesis (Doctor of Medicine)
Divisions:	Faculty of Health & Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	14 Dec 2017 09:58
Last Modified:	31 Oct 2024 07:01
DOI:	10.17638/03008673
Supervisors:	rhodes, JM ORCID: 0000-0002-1302-260X campbell, BJ ORCID: 0000-0002-7407-012X
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008673
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