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

During a specific milk fermentation process with <i>Bifidobacterium breve</i> C50 and <i>Streptococcus thermophilus</i> 065 (Lactofidus<sup>TM</sup>), postbiotics with possible immunomodulatory properties are produced. We investigated the effects of this fermentat...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/9/3/254
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author 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
author_facet 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
author_sort Veronica Ayechu-Muruzabal
collection DOAJ
description During a specific milk fermentation process with <i>Bifidobacterium breve</i> C50 and <i>Streptococcus thermophilus</i> 065 (Lactofidus<sup>TM</sup>), 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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spelling doaj.art-3c11a1001d9245208010ba28dd97384d2023-11-21T10:20:13ZengMDPI AGVaccines2076-393X2021-03-019325410.3390/vaccines9030254A 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 RatiosVeronica Ayechu-Muruzabal0Ling Xiao1Tjalling Wehkamp2Ingrid van Ark3Elisabeth J. Hoogendoorn4Thea Leusink-Muis5Gert Folkerts6Johan Garssen7Linette E. M. Willemsen8Belinda van’t Land9Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The NetherlandsDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsDuring a specific milk fermentation process with <i>Bifidobacterium breve</i> C50 and <i>Streptococcus thermophilus</i> 065 (Lactofidus<sup>TM</sup>), 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.https://www.mdpi.com/2076-393X/9/3/254postbioticsvaccinationinfluenzagalectinsfermentationadaptive immunity
spellingShingle 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
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
Vaccines
postbiotics
vaccination
influenza
galectins
fermentation
adaptive immunity
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic postbiotics
vaccination
influenza
galectins
fermentation
adaptive immunity
url https://www.mdpi.com/2076-393X/9/3/254
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