Date of Award

2021-05-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Charles T. Spencer

Abstract

Francisella tularensis is intracellular bacteria which is the causative agent of the disease Tularemia. Highly virulent in both humans and animals, it takes only as few as 10 microorganisms to cause a lethal infection. The bacteria can enter via direct or indirect routes causing the activations of the host innate inflammatory response to ensue. The bacteria invade host dendritic cells and neutrophils but predominately macrophages. This causes a mass inflammatory response resulting in the cytokine storm. Activation of Natural Killer T (NKT) cells has been shown to suppress inflammation in in vivo studies. Development and optimization of an in vitro co-culture assay were used to isolate NKT cell bulk purified populations from other cell types. Bulk purified NKT cells directly suppressed the production of inflammatory cytokines from Francisella tularensis-infected macrophages. This was attributed to a cell contact dependent mechanism that seemed in involve CD40/CD40L interactions. The bulk NKT cell population contains two subsets described by their antigen recognition and effector mechanism. Further separations showed that the type I NKT subset inhibited Il-6 secretion and suppressed inflammation in a dose dependent manner in vitro. Further studies are needed to fully characterize the inhibitory properties of type I and type II NKT cell subsets in Francisella tularensis immunity.

Language

en

Provenance

Received from ProQuest

File Size

45 p.

File Format

application/pdf

Rights Holder

Nicole Renee Setzu

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