Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the 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 an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.
Highlights
Responsible for estimated losses exceeding US$600 million/year in the USA alone, porcine reproductive and respiratory syndrome (PRRS) is a devastating disease in the swine industry [1]
In an attempt to uncover new mechanisms whereby macrolides may protect against the detrimental effects of porcine reproductive and respiratory syndrome virus (PRRSV), the present study investigated the effects of tulathromycin in porcine monocyte-derived macrophages
Treatment options to control PRRS outbreaks are limited and the efficacy of vaccines is thwarted by the antigenic variability of PRRSV [51]
Summary
Responsible for estimated losses exceeding US$600 million/year in the USA alone, porcine reproductive and respiratory syndrome (PRRS) is a devastating disease in the swine industry [1]. The virus targets alveolar macrophages (AM) [7, 8], and is able to infect most cells of the monocyte-macrophage lineage such as intravascular and lymph node macrophages [7, 9, 10] These cells play a crucial role in immune surveillance, pathogen killing and adaptive immune response stimulation [11]. Opportunistic pathogens, whether viral—swine influenza virus, pseudorabies virus- or bacterial– Streptococcus suis, Bordetella brochiseptica—potentiate PRRSV-induced pneumonia [14] These synergistic effects promote a self-sustaining inflammatory response increasing the severity and the duration of the disease [17,18,19,20,21]
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