Applications of acute inflammation in livestock immunity

• Author / Creator

  More Bayona, Juan

• Higher vertebrates share multiple mechanisms of immune defences; however, evolutionarily divergent species display unique characteristics to achieve immunity. Although significant knowledge regarding acute inflammation comes from studies in classical models, understanding of distinct immune features in livestock is limited. Hence, my overall goal was to provide a deeper understanding of cellular processes during acute inflammation in livestock animals, and subsequently applying this knowledge to evaluate the effects of drinking water contaminants on early and long-term immune responses. My findings demonstrated that the peritoneal (abdominal in poultry) challenge model represents a reliable tool for assessing pro-inflammatory and pro-resolving phases of acute inflammation in swine and poultry. This model allows analysis of resident leukocytes to evaluate antimicrobial responses under ex vivo exposure and the study of cellular functions following in vivo challenge. Taking advantage of high-resolution imaging and cell-sorting flow cytometry along with antibody-based and conventional staining, I established an approach for characterization of acute inflammation and the transition to adaptive immunity in livestock. This self-resolving challenge model in poultry based on zymosan, displayed different dynamics of antimicrobial responses compared to other vertebrates. This showcased that chickens mount distinct immune responses against pathogens compared to mammals, while heat-killed Salmonella enterica serovar Typhimurium (HKST) induced a more conserved self-resolving model in swine compared to other vertebrates. Nevertheless, major differences were observed in the antimicrobial and functional level at resolving phases of inflammation. For instance, peritoneal leukocytes displayed higher levels of reactive oxygen species (ROS) at 4 h post challenge and gradual decrease up to 48 h in swine. In contrast, poultry showed maximum ROS proportions at 12 h and decreased up to 48 h following zymosan challenge. Additionally, apoptotic leukocytes promoted distinct inflammatory downregulation in poultry compared to mammals and lower vertebrates. Altogether, this demonstrates the distinct mechanisms in avian and swine immune function during acute inflammation. In non-industrialized farms, use of untreated underground water is linked to the occurrence of several problems in exposed animals. I wanted to address, the extent to which, water contaminants diminish the immune capacity of livestock to battle infections. To this purpose, I used raw well water from small farms in areas of potential environmental pollution in Alberta, Canada. The objective was to evaluate whether drinking water contaminants altered immune responses following an in vivo challenge in poultry and swine. My results showed that water contaminants altered the homeostatic immunological status and the acute inflammation in both poultry and swine. In chickens, short-term exposure to raw well water increased KUL01+ cells and their ROS production capacity under zymosan (fungal) exposure, but not with GFP-Salmonella enterica serovar Typhimurium (GFP-ST). Additionally, it downregulated nitric oxide production in heterophils when challenged with zymosan, whilst altered dynamics of leukocyte subsets with HKST. In swine experiments, in addition to raw well water, I included a spiked water treatment. This contained a combination of raw water, sulfolene and diesel oil to evaluate their combinatorial effect on immune responses. Homeostatic (prior to HKST challenge) levels of ROS production were downregulated while NF-κB translocation were higher in spiked water. Following HKST challenge, the neutrophil pool remained higher even at 48 h post HKST challenge in this spiked group, while monocyte/macrophage and lymphocytes pools remained lower at 12 and 48 h compared to control group. Levels of ROS production were unaffected by water contaminants. However, NF-κB activation was downregulated as early as 12 h post challenge. Taken together, this reveals that water contaminants induced a prolonged inflammatory leukocytes migration in poultry and swine. This suggested alterations in the timely return to homeostasis and effects in the development of the long-term immunity. Indeed, following 2 and 4 weeks, water contaminants differentially altered development and antimicrobial function of circulating monocytes and lymphocytes. This demonstrates that water contaminants have impacts the development of adaptive immunity in swine and poultry. Altogether this thesis provides additional understanding of the mechanistic processes during acute inflammation in poultry and swine establishing divergent mechanisms to battle pathogens. Furthermore, it describes combinatorial effects of water contaminants in the progression of acute inflammation into long-term immunity. Lastly, this thesis offers a platform of immunoassays that can be useful for assessment of immune performance in livestock.

• Subjects / Keywords

  • acute inflammation
  • poultry immunity
  • livestock
  • swine immunity

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-677p-rv63

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.