Lipopolysaccharide Downregulates CD163 Expression to Inhibit PRRSV Infection via TLR4-NF-κB Pathway

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to induce proinflammatory cytokine production and modulate the host interferon (IFN) system. Proinflammatory cytokines and type I IFNs contribute to the prevention of viral infection. Lipopolysaccharide (LPS), a specific agonist to Toll-like receptor 4 (TLR4), provokes signal transduction and activates immune response in vivo and in vitro. Here we identified LPS inhibited PRRSV infection in porcine alveolar macrophages (PAMs) and in Marc-145 cells. To investigate the possible mechanism, we found TLR4-NF-κB pathway was obviously activated in LPS-treated PAMs at the early stage of PRRSV infection. As a result, the expression of proinflammatory cytokines was strongly induced following LPS and PRRSV co-treatment. Due to the enhanced proinflammatory response, CD163 expression was significantly reduced and a disintegrin and metalloproteinase 17 was activated, which promotes the cleavage of membrane CD163. Ultimately, CD163 down-regulation led to the suppression of PRRSV replication. Our data demonstrate that LPS has an impact on PRRSV infection via inflammation response, which provides a new insight of inflammation-mediated antiviral immunity and a new strategy to control PRRSV infection.

Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2) Promotes M1 Repolarization of Porcine Alveolar Macrophages and Th1 Type Response

“…Overexpression of CD163 contributes to the susceptibility of non-permissive cell lines to PRRSV infection. By binding to the three structural proteins GP2, GP4 and GP5, CD163 mediates entry and attachment of the virus to susceptible host cells [ 56 ].…”

Analyzing the Carotenoid Composition of Melilot (Melilotus officinalis (L.) Pall.) Extracts and the Effects of Isolated (All-E)-lutein-5,6-epoxide on Primary Sensory Neurons and Macrophages

“…The model systems we used for functional investigation of water-soluble cyclo-dextrine complex of (all- E )-lutein 5,6-epoxide refer to mechanisms involved in a broad range of nociceptive and inflammatory processes: TPRA1 activation is an important pathway of several inflammatory mediators and irritants on sensory neurons [ 12 , 13 ], and LPS-evoked Toll-like receptor 4 stimulation on macrophages mimics an important component of the inflammatory cascade [ 40 ].…”

Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

“…After treatment with TPA and LPS, CD163 expression on the cell membrane decreased, along with a reduction in PRRSV production [93]. Another study showed that treatment with LPS inhibited PRRSV infection in PAMs and MARC-145 cells [110]. Since the TLR4 (toll-like receptor 4)-NF-κB (nuclear factor-kappa B) pathway is activated in LPS-treated cells at the early stage of PRRSV infection, proinflammatory cytokines were strongly induced and subsequently reduced the CD163 expression.…”