Semester

Summer

Date of Graduation

2021

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Animal and Nutritional Sciences

Committee Chair

Scott Bowdridge

Committee Co-Chair

Jianbo Yao

Committee Member

Rosana Schafer

Committee Member

Vagner Benedito

Committee Member

Kimberly Barnes

Abstract

Little is known about differences observed in early immunological signaling events that result in cellular infiltration and Th2 cytokine production that mediate parasite expulsion. Parasite resistant St. Croix (STC) sheep have been used as model for full host protective immunity as they present the ability to respond to larval stages of H. contortus. RNA sequencing analysis of peripheral blood mononuclear cells (PBMC) stimulated with H. contortus larval antigen (HcLA) revealed significant upregulation in NLRP3 and its pathway component TLR4. Predicted protein structural software identified distinct differences in NLRP3 protein structure in STC and parasite susceptible Suffolk (SUF) sheep. NLRP3 has been widely studied in a classic model of inflammatory infection, but little is known about its role in helminth infections. The inhibition of NLRP3 in a classic model of infection reduced STC PBMC responses on both the transcript and protein level but had no effect on the transcript level for SUF PBMC only the protein level. In an HcLA infection model PBMC from SUF with the inhibition of NLRP3 resulted in the upregulation of TLR4, TLR2, and IL-10. We hypothesize NLRP3 loss of function to have a significant impact on components of TLR4 signaling and inflammatory immune activation to pathogenic challenge. The inhibition of a dysfunctional NLRP3 receptor in SUF sheep maybe a potential target for chemotherapeutics to achieve full host protective immunity.

Comments

Due to COVID, both my candidacy exams and defense were virtual. As a result I have my forms completed however, they aren't signed by all committee members. My department has accepted email confirmation to Wendy Daly by committee members over this past year.

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