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  • http://hdl.handle.net/10048/1262
  • Antiviral and cytokine responses of human mast cells to influenza A virus infection
  • Marcet, Candy
  • en
  • mast
    antiviral
    influenza
    virus
    cytokine
  • Aug 12, 2010 2:38 PM
  • Thesis
  • en
  • Adobe PDF
  • 2842565 bytes
  • Mast cells are immune cells important in innate immunity. Besides their role in asthma and allergies, mast cells are critical effector cells against various pathogens. Mast cells are established to be protective against bacterial infections, but little is known about their functions in viral infections. Mast cells are abundant in the lungs where influenza A virus (FluA) enter the host. We measured mRNA transcription, protein translation, and synthesis of new viral particles in FluA-treated mast cells. While expression of FluA mRNA and proteins followed similar time courses in both mast cells and epithelial cells, mast cells released a near absence of FluA. We also studied mast cell cytokine release in response to FluA and other viral-associated stimuli such as TLR ligands and type I interferons. Mast cells released the cytokines IL-6 and TGF-, and chemokines CXCL8 and CCL5 in response to various viral stimuli. However, different stimuli were capable of inducing release of different mediator subsets, demonstrating the specificity of mast cell responses. Since FluA infection of mast cells produce little new FluA virions, we investigated whether FluA induces expression of antiviral proteins in mast cells. FluA treatment resulted in mast cell expression of antiviral proteins, namely myxovirus resistance protein A, protein kinase R, interferon stimulated gene 15, viral stress inducible protein 56, and endothelial nitric oxide synthase. Next, we performed co-culture experiments using FluA-infected epithelial cells with or without the addition of mast cells. Our results showed that mast cells in co-culture inhibited the expression of the viral hemagglutinin protein in FluA-infected epithelial cells. Also, preliminary results showed that addition of mast cells protected epithelial cells from FluA infection by limiting the release of FluA particles and reducing epithelial cell death. Our discovery that mast cells produce little virus and express antiviral proteins suggest that mast cells have antiviral mechanisms to restrict FluA infection. This concept was further supported by evidence that mast cells are protective against FluA infection in epithelial cells. This research provides a better understanding of mast cells in innate immunity and may reveal unique antiviral mechanisms valuable in the development of antiviral therapeutics.
  • Doctoral
  • Doctor of Philosophy
  • Department of Medicine
  • Fall 2010
  • Befus, A. Dean (Medicine)
  • Befus, A. Dean (Medicine)
    Adamko, Darryl (Pediatrics)
    Vethanayagam, Dilini (Medicine)
    Barry, Michele (Medical Microbiology and Immunology)
    Magor, Katharine E. (Biological Sciences)
    Marshall, Jean S. (Microbiology and Immunology, Dalhousie University)

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