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Phenotyping macrophages and function of monocytes in respiratory syncytial virus (RSV) infection

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Title: Phenotyping macrophages and function of monocytes in respiratory syncytial virus (RSV) infection
Authors: Affendi, Siti (Sarah)
Item Type: Thesis or dissertation
Abstract: ABSTRACT Respiratory syncytial virus (RSV) is a major cause hospitalization of children with respiratory illness worldwide. RSV infection can lead to severe bronchiolitis in some infants. This is characterised by excessive inflammation leading to airway occlusion. Therefore, understanding and managing inflammation in RSV disease is of great importance. Viral infection leads to activation and recruitment of innate cells into the airway and lungs which mediate the release of an array of cytokines and chemokines. Studies in murine model of influenza infection in the lung showed that recruited inflammatory monocytes promote pathology, but our knowledge of their role in RSV infection is limited. We hypothesized that inflammatory monocytes recruited from the bloodstream into the lung (rather than resident alveolar macrophages) contribute to inflammation during the early stages of RSV infection. Infecting mice with human A2 strain RSV, F4/80pos CD11bpos CD11cint Ly6Cpos inflammatory monocytes rather than resident F4/80pos CD11bneg CD11cpos Ly6Cpos alveolar macrophages predominated in the airway and lung on day 2 of RSV infection. The frequency of these cells decreased both in the airway and lungs at day 4 suggesting changing roles for different cell types during the evolving response to RSV infection. To determine the role of inflammatory monocytes, blood monocytes were depleted via intravenous injection of clodronate liposomes during RSV infection. This reduced numbers of F4/80pos CD11bpos CD11cint Ly6Cpos cells both in the airway and lung at day 4 and 7 compared to simple RSV infection. This depletion caused attenuated weight loss, suggesting reduction in lung pathology. Although there was an increase in NK cell number in the airway at day 4 and 7 post infection with monocyte depletion, CD4pos and CD8pos T-cell percentage and number were effected. We conclude that inflammatory monocytes profoundly affect the inflammatory responses to RSV infection and depleting them may be protective against RSV disease.
Content Version: Open Access
Issue Date: Oct-2014
Date Awarded: Mar-2015
URI: http://hdl.handle.net/10044/1/44526
DOI: https://doi.org/10.25560/44526
Supervisor: Openshaw, Peter JM
Culley, Fiona J
Sponsor/Funder: Maxis Communications Berhad
Wellcome Trust (London, England)
Funder's Grant Number: WHRR G00430
Department: National Heart & Lung Institute
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:National Heart and Lung Institute PhD theses



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