Claeys Manon S C, Brabant Simon G A L, Rosschaert Stijn, Van Waesberghe Cliff, Favoreel Herman W
Laboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Front Immunol. 2025 Jul 3;16:1596490. doi: 10.3389/fimmu.2025.1596490. eCollection 2025.
Pseudorabies virus is a porcine alphaherpesvirus that causes devastating disease with high mortality in young piglets but much milder, mainly respiratory, problems in older pigs. Here, we report marked age-dependent differences in the cytokine response profile of primary porcine peripheral blood mononuclear cells (PBMCs) to pseudorabies virus (PRV)-infected cells. Notably, IFN-α and IL-12 production in response to PRV remains low to almost undetectable in piglets up to 8.5 weeks of age, followed by a marked increase in older piglets, which coincides with age-related shifts in PRV symptomatology. Additionally, we found that PBMC from newborn piglets exhibit a high IL-6 and IL-10 production which, in combination with the low IL-12 levels, suggests a suppressed Th1 immune response, similar to neonatal humans and mice. Our results reveal a remarkable age-dependent difference in PBMC cytokine response to PRV and provide a basis to identify cytokines or adjuvants that shift the neonatal immune response towards a Th1 response, potentially improving outcomes of severe viral infections in the neonatal period in both pigs and humans.
伪狂犬病病毒是一种猪α疱疹病毒，可导致仔猪出现高死亡率的毁灭性疾病，但在成年猪中症状较轻，主要表现为呼吸道问题。在此，我们报告了原代猪外周血单个核细胞（PBMC）对伪狂犬病病毒（PRV）感染细胞的细胞因子反应谱存在明显的年龄依赖性差异。值得注意的是，在8.5周龄以下的仔猪中，PBMC对PRV产生的IFN-α和IL-12水平较低，几乎检测不到，而在大龄仔猪中则显著增加，这与PRV症状学的年龄相关变化相一致。此外，我们发现新生仔猪的PBMC表现出较高的IL-6和IL-10产生水平，结合低水平的IL-12，提示Th1免疫反应受到抑制，这与新生儿人类和小鼠相似。我们的结果揭示了PBMC对PRV的细胞因子反应存在显著的年龄依赖性差异，并为鉴定可将新生儿免疫反应转向Th1反应的细胞因子或佐剂提供了依据，这可能改善猪和人类新生儿期严重病毒感染的结局。
