Date of Graduation

Spring 5-23-2026

Document Type

Thesis

Degree Name

Master of Science in Biology

College/School

College of Arts and Sciences

Department/Program

Biology

First Advisor

Dr. Sangman Kim

Second Advisor

Dr. Naupaka Zimmerman

Third Advisor

Dr. Christina Tzagarakis-Foster

Abstract

Toll-like receptors are a class of innate immune pattern recognition receptors that detect pathogen-associated molecular patterns and regulate downstream inflammatory responses. Toll-like receptor 10 remains the only human TLR whose ligand specificity, cellular localization, and immunological function are not fully defined. Emerging evidence suggests that TLR10 may play an anti-inflammatory role and can heterodimerize with TLR2 to modulate immune signaling. Previous studies from our laboratory demonstrated that stimulation with heat-killed Mycobacterium tuberculosis promotes TLR2-TLR10 heterodimerization and trafficking to the cell surface. In this study, we expanded our ligand panel to include additional gram-positive bacteria, particularly anti-inflammatory probiotic species, to further investigate the functional role and localization of TLR10. HEK-Blue cells cotransfected with TLR2 and increasing levels of TLR10 were stimulated with Lactobacillus rhamnosus, Lactobacillus fermentum, Lactobacillus plantarum, and other probiotic lysates. Increasing TLR10 expression resulted in dose-dependent attenuation of NF-κB activation and IL-8 production, suggesting that TLR10 suppresses TLR2-mediated inflammatory responses to probiotic bacteria. To further characterize TLR10 localization, HEK293T cells transfected with TLR2, TLR10, or TLR2+10 were analyzed by flow cytometry under permeabilized and non-permeabilized conditions. Flow cytometry analyses demonstrated that TLR10 exhibited both plasma-membrane associated and intracellular localization patterns, suggesting dynamic shuttling distribution alongside TLR2 that was likely influenced by microbial-dependent stimulation. Together, these findings support a model in which TLR10 functions as a modulatory, anti-inflammatory receptor that limits TLR2-driven signaling and may contribute to immune tolerance toward commensal microbes. Although TLR10 remains understudied, this study aimed to further characterize the molecular mechanisms underlying its signaling, trafficking, and ligand recognition. By doing so, we sought to establish a foundation for future research in physiologically relevant immune cell systems.

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