Date of Award

August 2012

Degree Type

Thesis

Degree Name

Master of Science

Department

Biomedical Sciences

First Advisor

Dean T. Nardelli

Committee Members

Jeri-Annette Lyons, Janis T. Eells, Jennifer A. Doll

Abstract

Lyme arthritis is a devastating symptom of Lyme borreliosis that causes severe inflammation of the synovial joints. Interleukin-17 (IL-17) plays a role in the pathogenesis of various arthritides, including, possibly, Lyme arthritis, by causing the expression of genes involved in the production of inflammatory cytokines by synoviocytes. However, the cellular sources of IL-17 in the context of Borrelia burgdorferi infection are unknown, as are the effects of these cells on the development of arthritis and stimulation of humoral immunity through the production of borreliacidal antibodies. Using multiple models of Lyme arthritis, the hypothesis that IL-17 produced by CD4+ cells contributes to the inflammation associated with B. burgdorferi infection and is associated with an increase in borreliacidal antibody production was tested. Serum IL-17 levels were increased during Borrelia infection, especially at the time of peak swelling. Neutralization of interferon-gamma increased these IL-17 levels, and the addition of anti-CD4 antibodies to cultures of stimulated cells isolated during peak swelling reduced IL-17 levels. In addition, a role for IL-10 in the production of IL-17 was demonstrated. Furthermore, increased IL-17 was associated with an increase of borreliacidal antibodies. These findings suggest CD4+ cells (possibly T cells) contribute to the production of IL-17 following infection with B. burgdorferi and that levels of this cytokine may affect borreliacidal antibody production.

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