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|Title: ||Influenza virus infection in a compromised immune system|
|Authors: ||Campbell, Gillian Mhairi|
|Supervisor(s): ||Dutia, Bernadette|
|Issue Date: ||30-Jun-2012|
|Publisher: ||The University of Edinburgh|
|Abstract: ||Severe influenza virus infection, including human infection with highly
pathogenic H5N1 viruses is characterised by massive pulmonary inflammation,
immunopathology and excessive cytokine production, a process in which
macrophages may play a vital role. The aim of this project was to investigate
the hypothesis that inhibition of inflammatory responses from infected
macrophages, using either alternatively activated bone marrow derived
macrophages (BMDMf), or IFNg receptor deficient (IFNgR-/-) mice may
ameliorate the devastating immunopathology and inflammation routinely
observed in highly pathogenic influenza virus infections.
Infection of alternatively activated BMDMf resulted in enhanced positivity for
viral proteins, compared with classically activated, inflammatory BMDMf.
However, neither subset propagated the infection indicating that while
infection is abortive in both classical and alternatively activated BMDMf, the
latter may prove more efficient at removing infectious virus from the site of
infection due to enhanced infectivity. However, influenza virus was capable of
driving expression of proinflammatory mediators such as iNOS and TNFa from
classical and alternatively activated BMDMf even in the absence of IFNg
signalling. IFNgR-/- BMDMf demonstrated a reduced inflammatory response to
infection compared to Sv129 counterparts, suggesting a potentially impaired
inflammatory response in vivo.
This was investigated by infection of IFNgR-/- mice, which resulted in
ameliorated disease, lower viral titres and mild immunopathology,
demonstrating that inhibition of IFNg signalling limits the severity of disease.
Additionally, mRNA expression for key inflammatory mediators was reduced,
demonstrating that inhibition of the overwhelming inflammatory response to
influenza virus infection is beneficial to the host, resulting in protection from
immunopathology and improved prognosis, without impairing viral clearance.|
|Sponsor(s): ||Biotechnology and Biological Sciences Research Council (BBSRC)|
|Appears in Collections:||Royal (Dick) School of Veterinary Studies thesis and dissertation collection|
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