Date of Award

Winter 2006

Project Type

Thesis

Program or Major

Microbiology

Degree Name

Master of Science

First Advisor

Lisa Clark

Abstract

Bacterial sepsis and systemic inflammatory immune responses continue to be major causes of illness and death despite extensive research into the development of antimicrobial agents. There is a need for novel therapeutic reagents designed to modulate these responses. Toll-like receptor 2 plays a key role in the development of innate and adaptive immune responses to microbial products that interact with the receptor's extracellular leucine-rich repeat ligand-binding domain. In a preliminary study, five peptides were synthesized that bound to the leucine-rich repeat region of Toll-like receptor 2 (TLR2). We tested the hypothesis that the novel TLR 2 leucine rich repeat binding peptides affects TLR2-mediated immune function by examining the ability of the five peptides to induce the maturation of bone marrow derived-dendritic cells in vitro. The dendritic cells were cultured in the presence of the peptides and maturation was determined through flow cytometry and cytokine analysis. We discovered that dendritic cells produced interleukin-6 to the JT1 leucine-rich repeat binding peptide. Some activation of the MHC class II dendritic cell maturation marker was observed in response to peptide JT1. Our results indicate that the JT1 synthetic toll-like receptor 2 leucine rich repeat binding peptide induces maturation of bone marrow derived dendritic cells in vitro.

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