Respiratory syncytial virus (RSV) is the primary viral pathogen responsible for lower respiratory tract disease in neonates and young children worldwide. By the age of two, virtually all children have been infected with RSV, and approximately 40% of them develop lower respiratory tract infections. In addition to acute morbidity, an association between RSV infection in early childhood and later development of recurrent wheezing and airway hyperresponsiveness (AHR) has been repeatedly demonstrated.<p>In this work we established a method for propagating pneumonia virus of mice (PVM) in a baby hamster kidney-21 (BHK-21) cell line. We also modified the standard plaque assay method and established a reliable and, most importantly, reproducible way to quantitate PVM. In our work we used PVM strain 15 to successfully establish an in vivo animal model for RSV disease in Balb/c and C57/Bl mice. Different susceptibility/resistance patterns to a pathogen exist for different mouse strains. In the case of Balb/c and C57/Bl mice, these patterns are well characterized for several pathogens including Leishmania major and adenovirus type 1. Our comparative study demonstrated clear differences in susceptibility to PVM strain 15 infection between Balb/c and C57/Bl mice; Balb/c mice being more susceptible.<p> In peripheral sites, dendritic cells (DCs) serve as sentinel cells that take up and process antigens. Numerous studies revealed that certain pathogens stimulate changes in DC phenotypic characteristics and thus contribute to functional alterations that lead to inappropriate T cell activation and disease augmentation. To examine effects of PVM on DCs, we infected bone marrow dendritic cells (BM-DCs) derived from both mouse strains with PVM, and evaluated their phenotypic and functional characteristics 24 hours post infection. Under these experimental conditions, PVM infected BM-DCs did not show a significant increase in the expression of costimulatory and major histocompatibility complex class II (MHC II) molecules compared to uninfected controls. Furthermore, there were no changes in the ability of PVM-infected DCs to take up soluble antigen. The production of IL-12p70, the pivotal cytokine in the development of a Th1-type response, by the PVM-infected BM-DCs was not significantly different from uninfected cells. In addition, there was no significant impact of PVM infection on the ability of DCs to induce naïve T cell proliferation.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-07172008-085118 |
| Date | 21 July 2008 |
| Creators | Arsic, Natasa |
| Contributors | Townsend , Hugh, Singh, Baljit, Griebel, Philip J., Babiuk, Lorne A., van Drunen Littel-van den Hurk, Sylvia |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-07172008-085118/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0026 seconds