Flores-Villalva Susana, Reid Cian, Remot Aude, Gordon Stephen V, Meade Kieran G
School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland; CENID Fisiología, INIFAP. Querétaro, Mexico.
School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
Vet Immunol Immunopathol. 2023 Apr;258:110575. doi: 10.1016/j.vetimm.2023.110575. Epub 2023 Feb 20.
Vitamin D deficiency (VDD) is associated with enhanced susceptibility to multiple respiratory diseases in humans, including tuberculosis. However, the consequences of VDD for disease susceptibility in calves are unknown. Previously we developed a model to drive divergent circulating 25OHD concentrations in cattle, where animals were supplemented with vitamin D (vit D) from birth to 7 months of age. Calves in the control group (Ctl) received a diet containing a standard vit D concentration, whereas the vit D group (VitD) received a diet with the highest vit D concentration allowed under EU guidelines. Here, we assessed the microbicidal activity and immunoregulatory effect of divergent 25OHD circulating levels to Mycobacterium bovis BCG challenge ex-vivo. Blood samples from Ctl and VitD calves were taken at 1-, 3- and 7-months of age. 25OHD concentrations were significantly different at 7 months (but not at 1 or 3 months) with animals from the VitD group having higher serum levels. Differences in microbicidal activity followed the same pattern, with no significant differences observed at 1 and 3 months, but at 7 months a significant increase in the percentage of bacteria killed was detected. Furthermore, analysis of the reactive oxygen species (ROS) and nitric oxide (NO) in serum showed a higher production of ROS and NO in VitD-supplemented calves. In contrast, serum concentrations of IL-1β and IL-8 were significantly lower. A similar anti-inflammatory profile was observed after gene expression analysis, with a significant downregulation of a cluster of genes including IL1B, IL1R1, CXCL1, CXCL2, CXCL5, MMP9 and COX2 and an upregulation of CXCR1, CX3CR1 and NCF1, in VitD calves after BCG challenge relative to Ctl animals. Collectively, these results suggest that dietary vit D boosts antimicrobial and innate immune responses and thereby could improve host anti-mycobacterial immunity.
维生素D缺乏（VDD）与人类对多种呼吸道疾病（包括结核病）的易感性增加有关。然而，VDD对犊牛疾病易感性的影响尚不清楚。此前，我们开发了一种模型来促使牛的循环25羟基维生素D（25OHD）浓度产生差异，即从出生到7月龄给动物补充维生素D（vit D）。对照组（Ctl）的犊牛食用含有标准vit D浓度的日粮，而vit D组（VitD）的犊牛食用欧盟指南允许的最高vit D浓度的日粮。在此，我们评估了不同循环水平的25OHD对体外卡介苗（Mycobacterium bovis BCG）攻击的杀菌活性和免疫调节作用。在1月龄、3月龄和7月龄时采集Ctl和VitD犊牛的血样。7月龄时25OHD浓度有显著差异（1月龄和3月龄时无差异），VitD组动物的血清水平更高。杀菌活性的差异遵循相同模式，1月龄和3月龄时未观察到显著差异，但在7月龄时检测到被杀细菌百分比显著增加。此外，血清中活性氧（ROS）和一氧化氮（NO）的分析表明，补充vit D的犊牛中ROS和NO的产生更高。相比之下，白细胞介素-1β（IL-1β）和白细胞介素-8（IL-8）的血清浓度显著更低。基因表达分析后观察到类似的抗炎特征，卡介苗攻击后，相对于Ctl动物，VitD犊牛中包括IL1B、IL1R1、CXCL1、CXCL2、CXCL5、MMP9和COX2在内的一组基因显著下调，而CXCR1、CX3CR1和NCF1上调。总体而言，这些结果表明，日粮中的vit D可增强抗菌和固有免疫反应，从而可能改善宿主抗分枝杆菌免疫力。
