Date Approved

12-2020

Graduate Degree Type

Thesis

Degree Name

Health Sciences (M.H.S.)

Degree Program

Biomedical Sciences

First Advisor

Kristin R. Renkema

Second Advisor

Debra Burg

Third Advisor

Frank Sylvester

Academic Year

2020/2021

Abstract

The hygiene hypothesis predicts that certain environmental factors shape overall immune system function in animals and humans. While current specific pathogen free (SPF) mouse models are invaluable for studying the immune system, they have limitations for comparison with humans who have microbial exposures throughout their lifetimes. Several studies have shown that the composition of the immune system of SPF mice more closely resembles that of newborns, whereas the immune system from mice exposed to microbial pathogens more closely reflect adult immunity. In this study we have established a model using traditional SPF mice (“clean mice”) and SPF mice that were cohoused with pet store mice (CoH mice). The goal of establishing this model was to observe if the cells of the innate immune system are more numerous and activated in mice who have been exposed to more microbial challenges during their development. Additionally, the goal of the model is to establish a framework for studying macrophage activity in CoH mice, including the potential for macrophages to develop a “learned response” as is commonly seen in adaptive immunity.

The initial data demonstrated that CoH mice could be successfully infected with a variety of microbes, while the control SPF mice remained “clean” without the use of a BSL-3 facility. With regard to innate immunity, F4/80+ CD11b+ peritoneal macrophages were more abundant in the CoH mice than in the SPF mice. In addition, CoH mouse white blood cells and peritoneal macrophages had increased MHC-II+ expression when compared to SPF mice. Using our model, we propose ways to characterize innate immune cell activation profiles in clean and CoH mice in order to better understand how microbial experiences impact innate immune profiles and activation.

Available for download on Friday, March 18, 2022

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