Porcine Reproductive and Respiratory Syndrome Virus Infection and Modulates a Switch in Macrophage Polarization from M1 to M2 Through the Release of Soluble CD83

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important infectious disease of pigs, elicits poor innate and adaptive immune responses associated with immunosuppression and incomplete viral clearance in most of the pigs. Soluble CD83(sCD83), a secret from membrane CD83 in various immune cell populations, was involved in negatively regulating the immune response, such as inhibiting activity and function of DC as well as restrainig DC-mediated immune cell functions. Macrophages are one of the first lines of defense in the immune system against viruses, and macrophage polarization plays a crucial role in immune surveillance and immunoregulation. We speculate sCD83 may be a critical factor in the process of PRRSV- coordinated macrophage polarization. In this study, we found that PAMs infected by PRRSV inhibited M1 macrophage while enhancing M2 macrophage markers, which was accompanied by decreased pro-inflammatory TNF-α release and iNOS expression but augmented anti-inflammatory IL-10 release and Arg1 expression. Meanwhile, sCD83 incubation causes the same specific effects on 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 lose the suppression of M1 macrophage markers, in contrast, to restrict up-regulation of M2 macrophage markers. These findings suggest that PRRSV could modulate a switch in Macrophage Polarization from M1 to M2 by upregulating the secretion of CD83 and shed light on a new insight into the mechanism by which PRRSV modulates host immunity