Zhu Ying-Chun, Cao Xin-Ya, Pang Heng, Wang Ting-Ting, Li Chuan-Gang, Peng Jun
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China.
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, East China Scientific Experimental Station of Animal Pathogen Biology of Ministry of Agriculture and Rural Affairs, Tai'an, China.
Vet Microbiol. 2022 Sep;272:109498. doi: 10.1016/j.vetmic.2022.109498. Epub 2022 Jun 27.
Interleukin 4 (IL-4) plays a major role in T-lymphocyte development and is thought to be a central regulator as a cofactor in resting B-lymphocyte proliferation. Primary infection with porcine reproductive and respiratory syndrome virus (PRRSV) induces minimal IL-4 production, whereas an IL-4 response occurs in the peripheral blood of piglets reinfected by PRRSV. The locations and interaction partners for the massive volume of IL-4 triggered by PRRSV reinfection remain unclear. This study aimed to investigate the characteristics of IL-4 secretion and location changes in peripheral immune organs induced by PRRSV infection and reinfection. Our results show that PRRSV reinfection induced higher levels of IL-4 mRNA and protein expression in the peripheral immune organs (e.g., lymph node and spleen) and peripheral blood compared with PRRSV primary infection. Importantly, we found that, following PRRSV reinfection, an obvious large-scale migration of IL-4 occurred in the lymph nodes. During PRRSV primary infection, IL-4 was mainly concentrated around the lymphoid follicles and paracortical regions of the lymph node and also located in the marginal area and periarterial lymphatic sheath region of the spleen. During PRRSV reinfection, the now abundant IL-4 gathered into the lymphoid follicles of the lymph node and spleen. Notably, IL-4 changed its location state from scattered and sparse during primary infection to clinging to B lymphocytes in the lymphoid follicles during reinfection. During reinfection, IL-4 was often co-localized with T and B lymphocytes; furthermore, the percentages of several T lymphocyte subsets, N protein-specific antibody levels, and viral load in the peripheral blood or lymph tissues underwent remarkable variation. Another important finding of this study was that the numbers of B lymphocytes and T lymphocytes in the lymphoid nodes were significantly reduced after PRRSV infection or reinfection, presumably due to PRRSV-induced acute bone marrow failure and autophagy in thymic epithelial cells. This study revealed the characteristics of IL-4 migration and distribution in the peripheral lymph organs induced by PRRSV reinfection and provides valuable clues for further exploration of the interactions between IL-4, B lymphocytes, and T lymphocytes during PRRSV infection and reinfection.
白细胞介素4（IL-4）在T淋巴细胞发育中起主要作用，并且被认为是静息B淋巴细胞增殖过程中的一种作为辅助因子的核心调节因子。猪繁殖与呼吸综合征病毒（PRRSV）的初次感染诱导产生极少的IL-4，而再次感染PRRSV的仔猪外周血中会出现IL-4应答。PRRSV再次感染引发的大量IL-4的定位及其相互作用伙伴仍不清楚。本研究旨在调查PRRSV感染和再次感染诱导的外周免疫器官中IL-4分泌特征及定位变化。我们的结果表明，与PRRSV初次感染相比，PRRSV再次感染在外周免疫器官（如淋巴结和脾脏）及外周血中诱导产生更高水平的IL-4 mRNA和蛋白表达。重要的是，我们发现，PRRSV再次感染后，IL-4在淋巴结中发生明显的大规模迁移。在PRRSV初次感染期间，IL-4主要集中在淋巴结的淋巴滤泡和副皮质区周围，也位于脾脏的边缘区和动脉周围淋巴鞘区域。在PRRSV再次感染期间，此时大量的IL-4聚集到淋巴结和脾脏的淋巴滤泡中。值得注意的是，IL-4的定位状态从初次感染时的分散和稀疏变为再次感染时附着于淋巴滤泡中的B淋巴细胞。再次感染期间，IL-4常与T和B淋巴细胞共定位；此外，外周血或淋巴组织中几个T淋巴细胞亚群的百分比、N蛋白特异性抗体水平及病毒载量发生显著变化。本研究的另一个重要发现是，PRRSV感染或再次感染后，淋巴结中的B淋巴细胞和T淋巴细胞数量显著减少，推测这是由于PRRSV诱导的急性骨髓衰竭及胸腺上皮细胞自噬所致。本研究揭示了PRRSV再次感染诱导的外周淋巴器官中IL-4迁移和分布特征，并为进一步探索PRRSV感染和再次感染期间IL-4、B淋巴细胞和T淋巴细胞之间的相互作用提供了有价值的线索。
