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Analysis of mast cell mediated immune response to <i>Listeria monocytogenes</i>

dc.creatorMcCall-Culbreath, Karissa Denise
dc.date.accessioned2020-08-22T17:11:31Z
dc.date.available2010-07-16
dc.date.issued2008-07-16
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-06252008-160252
dc.identifier.urihttp://hdl.handle.net/1803/12691
dc.description.abstractThe á2â1 integrin is expressed on many cell types throughout the immune system. Expression of the á2â1 integrin on mast cells is required for the early innate immune response to Listeria monocytogenes. Interaction between the á2â1 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 á2â1 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 á2â1 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 á2â1 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-á, but not IFN-ã are á2â1 integrin-dependent. Additionally, there is a diminished antigen specific T cell response in mice lacking the á2â1 integrin, but clearance of a secondary Listeria infection is not affected in these animals. These studies define a role for the á2â1 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 á2â1 integrin may be important in the adaptive immune response. We demonstrate that there is a role for the á2â1 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.
dc.format.mimetypeapplication/pdf
dc.subjectListeria monocytogenes -- Immunology
dc.subjectListeria
dc.subjectC1q
dc.subjectinnate immunity
dc.subjectMast cells
dc.subjectintegrin
dc.titleAnalysis of mast cell mediated immune response to <i>Listeria monocytogenes</i>
dc.typedissertation
dc.contributor.committeeMemberAmbra Pozzi
dc.contributor.committeeMemberTerry Dermody
dc.contributor.committeeMemberMary Zutter
dc.contributor.committeeMemberTom Thomas
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorVanderbilt University
local.embargo.terms2010-07-16
local.embargo.lift2010-07-16
dc.contributor.committeeChairMark Boothby


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