Colonic Responses to Swine Dysentery in Pigs
Date
2022-04
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Abstract
Swine dysentery (SD) is an enteric infectious disease of grower-finisher pigs caused by the bacterium Brachyspira hyodysenteriae. The disease causes bloody diarrhea and mortality, but not all infected pigs are clinically affected. Experimental infection of pigs with this pathogen rarely produces bloody diarrhea with 100% success rate. To determine whether colonization with B. hyodysenteriae is sufficient for SD pathogenesis, deeper knowledge of colonic host defenses is required. This thesis hypothesizes that colonic defenses drive SD pathogenesis and clinical presentation, then tests this hypothesis by assessing histological grade of colitis, neutrophil and macrophage defenses, and mucus and microbiome composition in pigs experimentally challenged with B. hyodysenteriae. This thesis shows that some challenged pigs were not colonized with B. hyodysenteriae. Others were infected but did not show clinical signs of disease (non-diseased), while most were both infected and clinically affected (diseased). Diseased pigs were the only group to show bloody diarrhea, high pathogen load, histological colitis, colonic neutrophil infiltration, and mucus hypersecretion. These changes were not present in B. hyodysenteriae-infected pigs that did not develop bloody diarrhea. Furthermore, diseased pigs showed dysbiosis with alterations of colonic microbiome composition. Thus, we concluded that clinical signs of disease resulted from defects in colonic microbiome, neutrophil and mucus barrier defenses in the colon. Manipulation of these host defenses may be a promising new treatment strategy for SD. Immunomodulatory cathelicidin peptides, such as the murine cathelicidin CRAMP, are attractive candidates for new SD treatments. Here, we showed that a single intraperitoneal injection of CRAMP was well tolerated in uninfected pigs, and the animals remained clinically healthy. CRAMP treatment decreased neutrophil influx near the colonic epithelium and altered mucin glycosylation patterns by mobilizing sialylated mucins to colonic lumen. Future testing of doses and routes of administration of CRAMP in porcine infection models would determine the potential of this peptide to boost colonic defenses against B. hyodysenteriae. This thesis brings new insight into intestinal innate immune responses during SD, thus laying the groundwork for development of cathelicidin-based treatments against this increasingly antibiotic-resistant disease.
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Keywords
swine dysentery, Brachyspira hyodysenteriae, colitis, cathelicidin, CRAMP, mucosal immunity
Citation
Fodor, C. (2022). Colonic responses to swine dysentery in pigs (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.