Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.656542
Title: Role of atopy in interferon production in response to rhinovirus and Streptococcus pneumoniae infection in mild asthma
Author: Macintyre, Jonathan David Robert
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Abstract:
Asthma exacerbations result in significant morbidity and rhinoviruses (RVs) are largely responsible. Asthmatics have increased susceptibility to RV infections and defective RV-induced interferon (IFN) production in atopic asthmatics (AA) has been observed in human bronchial epithelial cells (HBECs) and bronchoalveolar lavage (BAL) cells. 70-90% of asthmatics are atopic. Whether the previously observed IFN deficiency is asthma- or atopy-specific is unknown. Asthmatics have increased risk of invasive disease with Streptococcus pneumoniae (Spn) and proinflammatory/antibacterial cytokines are protective against bacterial infections. IFNs are anti-viral cytokines, but models of Spn infection have demonstrated type I IFNs are protective. Investigation of toll-like receptors (TLRs) might delineate the signalling pathways involved in IFN/proinflammatory cytokine deficiencies further. This study hypothesised that RV, Spn and TLR stimulation of HBECs, BAL cells and peripheral blood mononuclear cells (PBMCs) would result in deficient IFN production in AA and non-atopic asthmatics (NAA), compared to atopic non-asthmatics (ANA) and non-atopic non-asthmatics (NANA). IFN and proinflammatory cytokine mRNA and protein expression was analysed by qPCR and the MesoScale Discovery platform. IFNs were induced in all cell types following stimulation with RVs and TLR3/7/8 agonists. No differences were observed between asthmatics or controls; thus the role of atopy in IFN deficiency is still uncertain. IFNs were not induced from Spn-stimulated cells. Anti-bacterial cytokines were induced in PBMCs stimulated with Spn, but no differences were observed between asthmatics or controls. HBECs responded to TLR1/2/6/4/5/9 stimulation with non-significant increases in anti-bacterial cytokines and type III IFNs. PBMCs responded to TLR1/2/6/4/5/9 stimulation with no induction of type I or III IFNs, but increases in anti-bacterial cytokine proteins. Deficiency in asthmatics was not observed. The lack of IFN/proinflammatory cytokine deficiency was suggested to be due to the asthmatics having relatively mild disease. Further studies in more severe forms of asthma are required to investigate these responses further.
Supervisor: Johnston, Sebastian; Kon, Onn Sponsor: Imperial College London ; Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.656542  DOI: Not available
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