Wahyuningtyas Rika, Lai Yin-Siew, Wu Mei-Li, Chen Hsin-Wei, Chung Wen-Bin, Chaung Hso-Chi, Chang Ko-Tung
Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan.
Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan.
Vaccines (Basel). 2021 Sep 10;9(9):1009. doi: 10.3390/vaccines9091009.
The polarization status of porcine alveolar macrophages (PAMs) determines the infectivity of porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV infection skews macrophage polarization toward an M2 phenotype, followed by T-cells inactivation. CD163, one of the scavenger receptors of M2 macrophages, has been described as a putative receptor for PRRSV. In this study, we examined two types of PRRSV-2-derived recombinant antigens, A1 (g6Ld10T) and A2 (lipo-M5Nt), for their ability to mediate PAM polarization and T helper (Th1) response. A1 and A2 were composed of different combination of , , and in full or partial length. To enhance the adaptive immunity, they were conjugated with T cells epitopes or lipidated elements, respectively. Our results showed that CD163 expression on PAMs significantly decreased after being challenged with A1 but not A2, followed by a significant increase in pro-inflammatory genes (, , and ). In addition, next generation sequencing (NGS) data show an increase in T-cell receptor signaling in PAMs challenged with A1. Using a co-culture system, PAMs challenged with A1 can induce Th1 activation by boosting IFN-γ and secretion and expression. In terms of innate and T-cell-mediated immunity, we conclude that A1 is regarded as a potential vaccine for immunization against PRRSV infection due to its ability to reverse the polarization status of PAMs toward pro-inflammatory phenotypes, which in turn reduces CD163 expression for viral entry and increases immunomodulation for Th1-type response.
猪肺泡巨噬细胞（PAMs）的极化状态决定了猪繁殖与呼吸综合征病毒（PRRSV）的感染性。PRRSV感染会使巨噬细胞极化偏向M2表型，随后导致T细胞失活。CD163是M2巨噬细胞的清道夫受体之一，已被描述为PRRSV的假定受体。在本研究中，我们检测了两种PRRSV - 2衍生的重组抗原A1（g6Ld10T）和A2（lipo - M5Nt）介导PAM极化和T辅助（Th1）反应的能力。A1和A2由不同组合的全长或部分长度的[此处原文缺失具体成分信息]组成。为增强适应性免疫，它们分别与T细胞表位或脂化元件偶联。我们的结果表明，用A1而非A2刺激后，PAMs上的CD163表达显著降低，随后促炎基因（[此处原文缺失具体基因信息]、[此处原文缺失具体基因信息]和[此处原文缺失具体基因信息]）显著增加。此外，新一代测序（NGS）数据显示，用A1刺激的PAMs中T细胞受体信号增加。使用共培养系统，用A1刺激的PAMs可通过增强IFN - γ和[此处原文缺失具体分泌物质信息]分泌以及[此处原文缺失具体表达物质信息]表达来诱导Th1激活。在固有免疫和T细胞介导的免疫方面，我们得出结论，A1因其能够将PAMs的极化状态逆转至促炎表型，进而降低用于病毒进入的CD163表达并增强Th1型反应的免疫调节作用，被视为一种针对PRRSV感染进行免疫接种的潜在疫苗。
