Date of Award

Fall 9-6-2018

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Constantine Bitsaktsis, Ph.D.

Committee Member

Allan Blake, Ph.D.

Committee Member

Heping Zhou, Ph.D.

Keywords

T helper, Th17, Fc receptor, FcR-targeting, Francisella tularensis, vaccine development

Abstract

Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we focus specifically on a subpopulation of T helper (TH) lymphocytes by using C57BL/6 wild-type mice as an in vivo model for immunization and F. tularensis infection. Mice were immunized using fixed bacteria (iFt) or immune complexes (mAb-iFt) followed by a lethal dose of F. tularensis live vaccine strain (LVS) administered intranasal. Our data suggests that Th17 cells (characterized as CD3+/CD4+/IL17A+/RORγT+ cells), a T-lymphocyte subpopulation involved in pathology during autoimmunity but also protection against infectious diseases, was significantly increased in mAb-iFt immunized mice compared to mice immunized with iFt alone. Furthermore, the increased levels of IL17A, a cytokine predominantly secreted by Th17 cells, in the mAb-iFt immunized groups suggests a protective role played by this T lymphocyte subpopulation in this F.tularensis vaccine model.

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