A Fermented Milk Matrix Containing Postbiotics Supports Th1- and Th17-Type Immunity In Vitro and Modulates the Influenza-Specific Vaccination Response In Vivo in Association with Altered Serum Galectin Ratios

含有后生元的发酵乳基质可在体外支持 Th1 和 Th17 型免疫,并在体内调节流感特异性疫苗接种反应,并与血清半乳糖凝集素比率的改变相关

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作者:Veronica Ayechu-Muruzabal, Ling Xiao, Tjalling Wehkamp, Ingrid van Ark, Elisabeth J Hoogendoorn, Thea Leusink-Muis, Gert Folkerts, Johan Garssen, Linette E M Willemsen, Belinda Van't Land

Abstract

During a specific milk fermentation process with Bifidobacterium breve C50 and Streptococcus thermophilus 065 (LactofidusTM), 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.

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