Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83.
Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83.
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DOI：
10.3390/v15030773
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发表时间：
2023-03-17
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Gong X;Ma T;Zhang Q;Wang Y;Song C;Lai M;Zhang C;Fang X;Chen X
猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）是一种严重危害猪健康的传染病。可溶性CD 83（sCD 83）是来自各种免疫细胞群体（尤其是MoDC）的分泌物，其参与负调节免疫应答。我们推测sCD 83可能是PRRSV协同巨噬细胞极化过程中的一个关键因素。在这项研究中，我们发现PAM与PRRSV感染的MoDC共培养抑制M1巨噬细胞，同时增强M2巨噬细胞。这伴随着促炎细胞因子TNF-α和iNOS的减少以及抗炎细胞因子IL-10和Arg 1的增加。同时，sCD 83孵育引起相同的特异性效应，导致巨噬细胞从M1转换为M2。sCD 83的中和消除了PRRSV对PAM的抑制作用。利用反向遗传学，我们产生了N蛋白、nsp 1 α和nsp 10（敲除sCD 83相关的关键氨基酸位点）突变的重组PRRSV。四种突变病毒失去了对M1巨噬细胞标志物的抑制，与之相反的是对M2巨噬细胞标志物上调的限制。这些发现表明，PRRSV通过上调MoDC诱导的CD 83分泌来调节巨噬细胞极化从M1到M2的转换，为PRRSV调节宿主免疫的机制提供了新的见解。
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.
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