Characterization of vertebrate host immune responses to the lone star tick Amblyomma americanum (Acari: ixodidae)

Abstract

Amblyomma americanum, the lone star tick, is common throughout the southeastern United States and is known or suspected to vector the emerging pathogens Ehrlichia chaffeensis, E. ewingii, and Borrelia lonestari. In order to address the deficit of literature on immunomodulation of vertebrate hosts by A. americanum, we developed a murine model of A. americanum infestation and compared various immune parameters of infested and control animals. We found that infestation with nymphal A. americanum caused reductions in the proportions of CD+T cells and CD8+ T cells in the spleens, lymph nodes, and tick feeding lesions in mice, but no significant changes in T cell proliferation to mitogen or antigen. Infestation consistently increased the proportions of Type 2 cytokine positive cells and cytokine secretion and reduced IL-2+ cells and IL-2 secretion in mitogen and antigenstimulated spleen and lymph node cell cultures and cells taken directly from the bite site. In most experiments, infestation increased proportions of IFNã+ cells and/or secretion of IFNã in antigen- or mitogen-stimulated or directly assayed cells, which did not fit the Type 2 cytokine polarization model observed in other tick infestation studies. In infested mice, B cell populations were either unaffected or decreased in spleens and increased in lymph nodes, and levels of non-specific serum immunoglobulins (IgG1 and IgG2a) were decreased. Although some tick-induced changes were apparent on day 4, when ticks had just begun rapid engorgement, the greatest modulation of responses of infested mice was measured on day 7, when ticks had just finished feeding, and day 10, after all ticks had detached. The research presented in this dissertation is the first mouse model of A. americanum infestation, the first description of lymphocyte immunomodulation by A. americanum, the first study to measure tick modulation of antigen-specific changes using a transgenic host, the first study of tick immunomodulation by flow cytometry of intracellular cytokine production, and the first study to use flow cytometry to describe cellular responses at the tick bite site.