Ayechu-Muruzabal Veronica, Xiao Ling, Wehkamp Tjalling, van Ark Ingrid, Hoogendoorn Elisabeth J, Leusink-Muis Thea, Folkerts Gert, Garssen Johan, Willemsen Linette E M, Van't Land Belinda
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Danone Nutricia Research, 3584 CT Utrecht, The Netherlands.
Vaccines (Basel). 2021 Mar 13;9(3):254. doi: 10.3390/vaccines9030254.
During a specific milk fermentation process with C50 and 065 (Lactofidus), postbiotics with possible immunomodulatory properties are produced. We investigated the effects of this fermentation product (FP) in vitro using a model that allows crosstalk between intestinal epithelial (IEC) and immune cells. IECs were exposed to FP and αCD3/CD28-activated peripheral blood mononuclear cells after which the mediator secretion was measured. Additionally, using a murine influenza vaccination model, immune development was assessed. Mice were fed an AIN93G diet containing FP or lactose as control. Vaccine-specific immunity was measured as delayed-type hypersensitivity (DTH) and correlated to intestinal and systemic immunomodulation levels. In vitro, exposure to FP enhanced IFNγ, TNFα and IL-17A concentrations. Moreover, IEC-derived galectin-3/galectin-9 and galectin-4/galectin-9 ratios were increased. In vivo, dietary intervention with FP increased vaccine-specific DTH responses as compared to the lactose-receiving group. Although no effects on humoral immunity and vaccine-specific T-cell responses were detected, an enhanced systemic serum galectin-3/galectin-9 and galectin-4/galectin-9 ratio correlated with a shift in RORγ (Th17) mRNA expression over regulatory TGFβ1 in the ileum. This was also positively correlated with the increased DTH response. These results indicate that FP can enhance epithelial galectin-3 and -4 over galectin-9 release, and boost adaptive immunity by promoting Th1- and Th17-type cytokines under inflammatory conditions in vitro. Similar variations in galectin and immune balance were observed in the vaccination model, where FP improved the influenza-specific DTH response.
在使用C50和065(嗜乳酸杆菌)进行的特定牛奶发酵过程中,会产生具有潜在免疫调节特性的后生元。我们使用一种允许肠道上皮细胞(IEC)与免疫细胞相互作用的模型,在体外研究了这种发酵产物(FP)的作用。将IEC暴露于FP和αCD3/CD28激活的外周血单核细胞后,测量介质分泌。此外,使用小鼠流感疫苗接种模型评估免疫发育。给小鼠喂食含有FP或乳糖作为对照的AIN93G饮食。将疫苗特异性免疫作为迟发型超敏反应(DTH)进行测量,并与肠道和全身免疫调节水平相关联。在体外,暴露于FP可提高IFNγ、TNFα和IL-17A的浓度。此外,IEC衍生的半乳糖凝集素-3/半乳糖凝集素-9和半乳糖凝集素-4/半乳糖凝集素-9的比率增加。在体内,与接受乳糖的组相比,用FP进行饮食干预可增加疫苗特异性DTH反应。虽然未检测到对体液免疫和疫苗特异性T细胞反应的影响,但全身血清半乳糖凝集素-3/半乳糖凝集素-9和半乳糖凝集素-4/半乳糖凝集素-9比率的增加与回肠中RORγ(Th17)mRNA表达相对于调节性TGFβ1的变化相关。这也与DTH反应的增加呈正相关。这些结果表明,在体外炎症条件下,FP可增强上皮细胞半乳糖凝集素-3和-4相对于半乳糖凝集素-9的释放,并通过促进Th1型和Th17型细胞因子来增强适应性免疫。在疫苗接种模型中也观察到了半乳糖凝集素和免疫平衡的类似变化,其中FP改善了流感特异性DTH反应。