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dc.contributor.advisorMcConnell, Michelle
dc.contributor.advisorYoung, Sarah
dc.contributor.advisorHighton, John
dc.contributor.authorPeyroux, Estelle
dc.date.available2011-12-05T19:58:13Z
dc.date.available2011-12-05T20:21:12Z
dc.date.copyright2011
dc.identifier.citationPeyroux, E. (2011). Bowel Bacteria and Dendritic Cells in Ankylosing Spondylitis (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/2063en
dc.identifier.urihttp://hdl.handle.net/10523/2063
dc.description.abstractAnkylosing Spondylitis (AS) is chronic inflammatory arthritis of spine and sacroiliac joints with further peripheral manifestations. AS is a relatively common rheumatic disease affecting 0.1- 1.4% of the population. Early symptoms commence generally in the second decade of life, these include fatigue and pain which are managed by adherence to medication. Inflammation can result in fusion of the vertebrae in the spine. Susceptibility genes identified encode HLA-B27 and ERAP1 proteins, both essential components in antigen processing for immune response. An animal model of AS induced by the hla-B27 gene (present in 95% AS patients) indicated enteric bacteria triggers AS-like symptoms. Dendritic cells (DCs) are professional antigen presenting cells that direct immune responses. We generated monocyte-derived DCs (MoDCs) from venous blood of AS (n= 6) and control group (n= 8) and stimulated the cells with a range of gut bacteria- Bacteroides fragilis, Yersinia enterocolitica, Campylobacter jejuni and Helicobacter pylori. We measured expression of antigen presentation molecules MHC-I and MHC-II and CD83, a marker of activated DCs, by flow cytometry. Analysis of cytokine secretion in supernatants was assessed by Bioplex immunoassay. In addition to this preliminary experiments with inhibitors to MyD88 and TRIF adaptor molecules were used to identify the possible involvement of toll-like receptors in activation of DCs to bacterial treatments. The AS donors had a trend of lower basal expression of MHC-I and MHC-II. Our results indicated the level of MHC-I and MHC-II expression is significantly different (p< 0.0001) between AS and normal groups. The normal group’s up-regulation of MHC-I in response to C. jejuni was significantly greater (p= 0.03) compared to the AS group (p=0.1). Differences in MHC-II expression between AS and normal groups were just outside significance levels (p= 0.08) for both B. fragilis CAS10 and H. pylori treatments. CD83, a DC maturation marker, was expressed at similar levels for all AS-associated bacteria. H. pylori induced CD83 expression significantly (p= 0.03) in the normal group however the AS group did not up-regulate CD83 expression significantly (p= 0.2). Cytokine analysis showed a trend of decreased IL-12 and IL-10 production in AS-associated bacteria particularly in B. fragilis CAS10 and Y. enterocolitica. Our control bacteria, H. pylori, inversely induced higher IL-1β, IL-10 and IL-12. From these results we hypothesize that abnormal signaling through innate pattern recognition receptor signaling pathways induces aberrant activation of DCs in AS patients. These DCs in turn may direct cells of the immune system toward an inappropriate or misdirected immune response. We speculate that a low IL-10 production by DCs may result in a dysregulation of the immune response.
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectAnkylosing Spondylitis
dc.subjectDendritic Cells
dc.titleBowel Bacteria and Dendritic Cells in Ankylosing Spondylitis
dc.typeThesis
dc.date.updated2011-12-02T03:27:27Z
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.nameBachelor of Biomedical Sciences with Honours
thesis.degree.grantorUniversity of Otago
thesis.degree.levelHonours
otago.interloanno
otago.openaccessAbstract Only
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