Degree Type

Dissertation

Date of Award

2013

Degree Name

Doctor of Philosophy

Department

Animal Science

First Advisor

Christopher K. Tuggle

Second Advisor

Michael J. Wannemuehler

Abstract

Pork is the most highly consumed meat worldwide, and the swine industry generates $34.5 billion annually to the U.S. economy alone. Maintaining pork safety and minimizing production losses associated with swine disease impacts profitability, food safety and animal health. As such, the research presented herein focused on characterizing aspects of the porcine immune response to two challenges that impact swine health: swine barn dust exposure and Salmonella infection.

In the first set of experiments, swine barn organic dust extract (ODE) treatment negatively affected porcine macrophage phagocytosis, intracellular bacterial killing and NF-kB translocation. Further, ODE stimulated production of inflammatory cytokines and increased surface expression of CD163, the cellular receptor targeted by porcine reproductive and respiratory syndrome virus. Together, these results demonstrated ODE suppresses macrophage function, and implicate barn dust as a potential underlying cause of swine respiratory disease outbreaks.

Similar to the respiratory tract, the gastrointestinal tract is an interface of routine immune system exposure to a myriad of foreign antigens and pathogens. Salmonella enterica serovar Typhimurium enters the swine gut and can cause enteric disease, resulting in varied levels of fecal shedding from infected pigs. As these animals are often asymptomatic, the risk of disease transmission and pork contamination at slaughter is increased. The second set of experiments identified distinct immune response differences between low shedding (LS) and persistently shedding (PS) pigs experimentally inoculated with Salmonella enterica serovar Typhimurium (ST). The PS pigs had longer pyrexia and increased serum interleukin (IL) -1b, TNF-a, interferon (IFN) -g, and IL-12p40 at 2 days post-inoculation compared to non-inoculated controls, with up-regulation of genes in the blood involved in the STAT1, IFNB1 and IFNG regulation networks. The LS pigs had brief pyrexia, decreased fecal shedding more rapidly, and up-regulated genes involved in negative immune regulation as a component of their response.

The third set of experiments defined additional differences, characterizing the effects of ex vivo endotoxin stimulation in blood from LS and PS pigs. Endotoxin stimulation elicited similar inflammatory profiles from the blood of LS and PS pigs prior to inoculation with ST, with some differences in cytokine and gene expression responses. Differences between LS and PS were more evident on day 2 post-inoculation, as blood from PS pigs increased plasma IL-1b, TNF-a, IFN-g, CXCL8 and IL-10 as well as the expression of genes and networks involved in inflammation. Blood from LS pigs appeared to have an attenuated response to endotoxin stimulation post-inoculation, increasing only plasma TNF-a, CXCL8 and IL-10. Further, blood from the LS pigs had a dampened plasma IL-1b; response when compared to stimulation prior to inoculation, and up-regulated only 3 genes in response to endotoxin. These results demonstrate distinct differences in the blood response to ex vivo stimulation with endotoxin from pigs that differ in fecal ST shedding, providing potential tools for biomarker development to reduce swine disease and limit food safety risk.

Taken together, these three sets of experiments provide new findings to enhance the understanding of porcine immune response to an environmental and pathogenic challenge. Additionally, they provide insight into how these responses may shape disease outcome, with potential to assist in diagnostic and biomarker development as tools to improve swine health.

Copyright Owner

Susan Knetter

Language

en

File Format

application/pdf

File Size

279 pages

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