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Modification of the innate immune response during feline immunodeficiency virus infection

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dc.contributor.authorLehman, Tracy L., author
dc.contributor.authorAvery, Paul, advisor
dc.contributor.authorHoover, Edward, advisor
dc.date.accessioned2024-03-13T20:12:22Z
dc.date.available2024-03-13T20:12:22Z
dc.date.issued2008
dc.description.abstractLentiviruses such as the human immunodeficiency virus (HIV) and the feline immunodeficiency virus (FIV) have successfully evolved to both use and subvert the host innate and adaptive immune responses to establish long-term infections. Investigation into the mechanisms lentiviruses use to overcome host immune response allows the development of potential therapies and elucidates the intricacies of the immune response. Dendritic cells are professional antigen presenting cells that are intricately involved in innate immune responses and in coordinating the adaptive immune response. However, these same cells have been implicated in initial lentiviral infection, transfer of infection to other cells of the immune system, and alteration of the immune response to allow chronic and progressive infection of the host. To better understand the effects of lentiviral infection on myeloid dendritic cells (mDC), we used the FIV model and bone marrow-derived mDC to evaluate differences in growth, phenotype, and function. We found that chronic FIV infection did not affect mDC growth in culture, phenotype, or maturation as assessed by CD11c, MHC class II, CD80, and CD1a and ability to uptake dextran particles. However, mDC from FIV-infected cats were found to have significantly decreased ability to stimulate proliferation of allogeneic CD4+ T cells in the mixed leukocyte reaction. To begin a mechanistic examination of FIV-induced alteration of mDC function, we examined cytokine responses to Toll-like receptor (TLR) ligands and CD40L. We documented changes in the ratio of the immunoregulatory cytokines IL12 and IL10 in response to select TLR ligands and CD40L, which could result in impaired immune responses, impaired T cell interactions, and enhanced viral survival. Having identified alterations in DC function with FIV infection, we attempted to augment the antiviral effects of mDC by supplementing IL-12 levels in vivo using an adenoviral vector. Consistent with the known complexity of the immune response, increased IL12 levels proved toxic and thereby failed to be a viable means of enhancing the innate immune response to lentiviral infection. Our research documents functional changes induced in bone marrow-derived mDC by chronic FIV infection and provides a means of further investigation into the development, mechanisms, and therapies for those changes.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierETDF_Lehman_2008_3346462.pdf
dc.identifier.urihttps://hdl.handle.net/10217/237840
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.licensePer the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users.
dc.subjectbone marrow
dc.subjectdendritic cells
dc.subjectFIV
dc.subjectfeline
dc.subjectinnate immunity
dc.subjectlentivirus
dc.subjectmyeloid
dc.subjectanimal sciences
dc.subjectvirology
dc.subjectimmunology
dc.subjectanimal diseases
dc.titleModification of the innate immune response during feline immunodeficiency virus infection
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineMicrobiology, Immunology, and Pathology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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