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Neutrophils are one of the main effector cells of innate immunity and were shown to kill bacteria by phagocytosis more than 100 years ago. Neutrophils are also capable of antimicrobial activity by producing extracellular structures named neutrophil extracellular traps (NETs). This thesis is an investigation of porcine neutrophils and their ability to produce NETs, as well as the antimicrobial ability of secretions from activated porcine neutrophils in combating a variety of common porcine pathogens. Porcine neutrophils were found to produce NET-like structures, and secretions from activated neutrophils were found to possess variable bactericidal activity against common pathogens of swine. Antimicrobial proteins dependent on elastase activity were shown to be partially responsible for the bactericidal activities of activated neutrophils. Several antimicrobial proteins and peptides were identified via proteomic techniques. This work allows for better understanding of innate immunity in swine, and identification of potential targets for addressing porcine health. / Ontario Ministry of Agriculture Food & Rural Affairs, Ontario Pork, Natural Sciences and Engineering Research Council of Canada

Weaning piglets are susceptible to the invasive Streptococcus (S.) suis infection, which can result in septicemia. The aim of this study was to investigate the cytokine profile induced upon S. suis infection of blood, to determine the cellular sources of those cytokines, and to study the potential effects of the induced cytokines on bacterial killing. We measured TNF-α, IL-6, IFN-γ, IL-17A and IL-10 after an experimental intravenous infection with S. suis serotype 2 in vivo, and analyzed whole blood, peripheral blood mononuclear cells (PBMC) and separated leukocytes to identify the cytokine-producing cell type(s). In addition, we used a reconstituted whole blood assay to investigate the effect of TNF-α on bacterial killing in the presence of different S. suis-specific IgG levels. An increase in IL-6 and IL-10, but not in IFN-γ or IL-17A, was observed in two of three piglets with pronounced bacteremia 16 to 20 h after infection, but not in piglets with controlled bacteremia. Our results confirmed previous findings that S. suis induces TNF-α and IL-6 and could demonstrate that TNF-α is produced by monocytes in vitro. We further found that IL-10 induction resulted in reduced secretion of TNF-α and IL-6. Rapid induction of TNF-α was, however, not crucial for in vitro bacterial killing, not even in the absence of specific IgG.