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Title page for ETD etd-06252008-160252


Type of Document Dissertation
Author McCall-Culbreath, Karissa Denise
URN etd-06252008-160252
Title Analysis of mast cell mediated immune response to Listeria monocytogenes
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Mark Boothby Committee Chair
Ambra Pozzi Committee Member
Mary Zutter Committee Member
Terry Dermody Committee Member
Tom Thomas Committee Member
Keywords
  • Listeria monocytogenes -- Immunology
  • Listeria
  • C1q
  • innate immunity
  • Mast cells
  • integrin
Date of Defense 2008-05-07
Availability unrestricted
Abstract
The 􊁛 integrin is expressed on many cell types throughout the immune system. Expression of the 􊁛 integrin on mast cells is required for the early innate immune response to Listeria monocytogenes. Interaction between the 􊁛 integrin and Listeria occurs through C1q within a Listeria immune complex, but is not sufficient for activation suggesting an additional co-receptor is required for activation. We demonstrate that Listeria immune complex activation of mast cells occurs through crosstalk between the 􊁛 integrin and c-met. The best described mechanism of mast cell activation is IgE-mediated degranulation. We examined the mechanism of mediator release by mast cells following activation by Listeria immune complex. Activation by Listeria immune complex results in 􊁛 integrin-dependent release of IL-6 from a granule pool that is distinct from known mast cell granules, identifying a novel population of mast cell granules.

The 􊁛 integrin-dependent early innate immune response to Listeria suggested that the integrin modulate later steps in the innate immune response or adaptive immunity. We demonstrate that serum IL-6 and TNF-, but not IFN- are 􊁛 integrin-dependent. Additionally, there is a diminished antigen specific T cell response in mice lacking the 􊁛 integrin, but clearance of a secondary Listeria infection is not affected in these animals.

These studies define a role for the 􊁛 integrin and c-met in a novel mechanism of mast cell activation. Our studies also identify a pool of granules that contains IL-6 and can be selectively and differentially released following specific stimulation. Several studies have suggested that the 􊁛 integrin may be important in the adaptive immune response. We demonstrate that there is a role for the 􊁛 integrin in pro-inflammatory cytokine production and peak levels of antigen specific T cells, however we did not observe a defect in bacterial clearance or response to secondary infection. These studies provide a foundation for studies of the biology of mast cell mediator release and its role in modulation immune response.

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