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Porcine Circovirus Type 2 Induces Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Downregulation to Promote Interleukin-1β Upregulation in Porcine Alveolar Macrophage

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State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Innovative Team for GI Infection and Mucosal Immunity of Swine and Poultry, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
2
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yanzhou 225009, China
*
Authors to whom correspondence should be addressed.
Viruses 2019, 11(11), 1021; https://doi.org/10.3390/v11111021
Received: 16 October 2019 / Revised: 31 October 2019 / Accepted: 1 November 2019 / Published: 3 November 2019
(This article belongs to the Section Animal Viruses)
Multisystemic inflammation in pigs affected by porcine circovirus type 2 (PCV2) indicates the disordered expression of inflammatory cytokines. However, the PCV2-induced expression profile of inflammation cytokines and its regulating mechanism remain poorly understood. In this study, inflammatory cytokines and receptors in porcine alveolar macrophages (PAMs) after PCV2 infection were profiled in vitro by an RT2 ProfilerTM PCR array assay. The regulatory mechanism of interleukin-1β (IL-1β) expression was investigated. Results showed that 49 of 84 inflammation cytokines and receptors were differentially expressed (p < 0.05, absolute fold change ≥2) in PAMs at different stages post-PCV2 infection. Moreover, the overexpression of single-immunoglobulin interleukin-1 related receptor (SIGIRR) or the blocking of NF-κB activation by its inhibitor markedly decreased IL-1β secretion. This finding suggested that PCV2-induced overexpression of IL-1β was associated with the downregulation of SIGIRR and the activation of NF-κB. Furthermore, the excessive activity of NF-κB in SIGIRR-knockout PAMs cell line, indicating that SIGIRR negatively regulated IL-1β production by inhibiting the activation of NF-κB. Overall, PCV2-induced downregulation of SIGIRR induction of NF-κB activation is a critical process in enhancing IL-1β production in PAMs. This study may provide insights into the underlying inflammatory response that occurs in pigs following PCV2 infection.
Keywords: porcine circovirus type 2; porcine alveolar macrophage; inflammatory cytokines; single-immunoglobulin interleukin-1 related receptor (SIGIRR); IL-1β porcine circovirus type 2; porcine alveolar macrophage; inflammatory cytokines; single-immunoglobulin interleukin-1 related receptor (SIGIRR); IL-1β
MDPI and ACS Style

Yang, S.; Liu, B.; Yin, S.; Shang, Y.; Zhang, X.; Khan, M.U.Z.; Liu, X.; Cai, J. Porcine Circovirus Type 2 Induces Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Downregulation to Promote Interleukin-1β Upregulation in Porcine Alveolar Macrophage. Viruses 2019, 11, 1021.

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