Date of Award
Master of Science (MS)
Bordetella pertussis, Dendritic cells, Imprinting, Lymphocyte Trafficking, Whooping cough
Biology, Molecular; Health Sciences, Immunology
Bordetella pertussis is an aerobic gram-negative bacterial pathogen that causes the human respiratory disease whooping cough. Despite widespread vaccination, whooping cough is reemerging due to decreased vaccine efficacy. One of the hallmarks of infection is lymphocytosis, which is induced by the pertussis toxin. Lymphocytes such as CD4+ T cells navigate to infected tissues through surface-trafficking molecules, which are imprinted during their interaction with tissue-associated dendritic cells. We hypothesized that the pertussis toxin affects the imprinting process resulting in altered expression of trafficking molecules on CD4+ T cells. We tested this hypothesis using a mouse model of infection. Imprinting levels on CD4+ T cells were compared to Bordetella parapertussis, a related strain that lacks pertussis toxin. Our results indicated that 5 days post-infection, the percentage of lung dendritic cells increased and adopted a mature phenotype (displaying an increased capability to migrate and present antigen to T cells) in response to B. pertussis infection, and there was an overall downregulation of trafficking molecules on CD4+ T cells. However, 25 days post-infection with B. pertussis, dendritic cells continued to express elevated levels of MHC class II, and the expression of trafficking markers on CD4+ T cells also increased compared to uninfected controls. These results enable identification of molecules that are specific for lymphocyte trafficking to the respiratory airways and contribute to knowledge useful in the development of better vaccines.
Waheed, Sana, "The effects of Bordetella pertussis on dendritic cell imprinting of CD4+ T cells" (2010). Master's Theses. Paper 3837.