Date of Graduation

Spring 5-18-2024

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. Brian Thornton

Third Advisor

Dr. Christina Tzagarakis-Foster

Abstract

Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (M. tb), is a leading global health crisis causing millions of cases and deaths each year. Though it affects individuals of any race, ethnicity, or cultural group, research shows the disease disproportionately affects individuals with Asian ancestry. Immunity to M. tb starts with its recognition by pattern recognition receptors such as Toll-like receptors (TLRs), which are key players in immune responses. TLR-10, an understudied toll-like receptor due to its inability to be studied through mouse models, is thought to play a key role in the clearance of inflammatory diseases. SNP I775V, a mutation in the TIR signaling domain of TLR-10 protein, has been shown to influence TB susceptibility and is highly prevalent among Asian populations. This study investigates TLR-10 mutations in relation to TB susceptibility by focusing on SNPs I775V and I473T. This was achieved by measuring NF-kB activity and inflammation-associated cytokine production in response to M. tb infection of WT and MUT TLR-10-transfected HEK293T cells. Though preliminary results indicated no difference in NF-kB activity in cells infected with heat-killed M. tb, subsequent examination of TLR-10 with Listeria monocytogenes elicited high levels of NF-kB activity and pro-inflammatory cytokine secretion– indicating a possible activation of alternative anti-inflammatory pathways in response to M. tb. FRET analysis revealed that TLR-10 has the capacity to dimerize with TLR-2, providing additional evidence that TLR-10 indeed participates in the M. tb immune response. Although TLR 10 is understudied, this study aims to shed light on its role in the clearance of inflammatory diseases.

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