Affiliation:
1. Institute of Cellular and Molecular Biology, School of Life Science, Jiangsu Normal University, Xuzhou 221116, China
2. College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266000, China
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important infectious disease of pigs, elicits poor innate and adaptive immune responses. Soluble CD83 (sCD83), a secretion from various immune cell populations, especially MoDCs, is involved in negatively regulating the immune response. We speculate sCD83 may be a critical factor in the process of PRRSV-coordinated macrophage polarization. In this study, we found that PAMs co-cultured with PRRSV-infected MoDCs inhibited the M1 macrophage while enhancing the M2 macrophage. This was accompanied by a decrease in the pro-inflammatory cytokine TNF-α and iNOS and an increase in the anti-inflammatory cytokine IL-10 and Arg1. Meanwhile, sCD83 incubation causes the same specific effects lead to a switch in macrophage from M1 to M2. Neutralization of sCD83 removes the inhibitory effects of PRRSV on PAMs. Using reverse genetics, we generated recombinant PRRSVs with mutations in N protein, nsp1α, and nsp10 (knockout sCD83-concerned key amino acid site). Four mutant viruses lost the suppression of M1 macrophage markers, in contrast to the restriction of the upregulation of M2 macrophage markers. These findings suggest that PRRSV modulates the switch of macrophage polarization from M1 to M2 by upregulating the MoDC-induced secretion of CD83, providing new insights into the mechanism by which PRRSV regulates host immunity.
Funder
Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Key Research and Development Plan (Modern Agriculture) Project of Xuzhou City
Subject
Virology,Infectious Diseases
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