Buret, Andre G.Desmonts de Lamache, Dimitri2018-08-132018-08-132018-08-10Desmonts de Lamache, D. (2018). Immuno-Modulating Properties of Tulathromycin in Porcine Reproductive and Respiratory Syndrome Virus-Infected Macrophages In Vitro. University of Calgary, Calgary, ABDesmonts de Lamache, D. (2018). Immuno-Modulating Properties of Tulathromycin in Porcine Reproductive and Respiratory Syndrome Virus-Infected Macrophages In Vitro (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32808http://hdl.handle.net/1880/107626With a total cost of productivity losses estimated at $600 million annually in the U.S alone, porcine reproductive and respiratory syndrome (PRRS) is a major concern in the swine industry. PRRS etiological agent, the porcine reproductive and respiratory syndrome virus (PRRSV) is a small positive-strand RNA virus that primarily grows in alveolar macrophages. Due to its high antigenic variability, and poorly understood immunopathogenesis, there is currently no treatment to control PRRSV infection. Commercially available vaccines are inefficient and cannot meet practical needs encouraging more researchers to explore different approaches to treat PRRSV infections. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics for the treatment of the disease it causes. Tulathromycin (TUL), a macrolide antibiotic previously studied in our laboratory has been shown to exhibit potent anti-inflammatory and immunomodulatory actions in cattle and pigs. The aim of this study was to identify and characterize anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as a cellular model to study PRRSV pathogenesis. TUL was found to not change viral titers and viral receptors (CD163 and CD169) expression suggesting that the drug does not possess direct antiviral effects against PRRSV. In addition, we showed that TUL acts synergistically with PRRSV to induce apoptosis but prevents virus-induced early necrosis. TUL was also found to attenuate PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevent phagocytosis inhibition. Together, these data demonstrate that tulathromycin downregulates PRRSV-induced inflammatory response in macrophages which may in turn reduce virus-related tissue injury. More importantly, this study sheds the light on the potential clinical benefits of an antibiotic in the context of a virus-induced inflammation.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.AntibioticsVirusTulathromycinPRRSVPigsBiologyVeterinary ScienceHealth Sciencesmaster thesis10.11575/PRISM/32808