Abstract
Prophylactic vaccinations are generally performed to protect naïve individuals with or without suppressed immune responsiveness. In a mouse model for Influenza vaccinations the specific alterations of CD4+CD25+Foxp3+ regulatory T-cells (Tregs) in the immune modulation induced by orally supplied oligosaccharides containing scGOS/lcFOS/pAOS was assessed. This dietary intervention increased vaccine specific DTH responses. In addition, a significant increased percentage of T-bet+ (Th1) activated CD69+CD4+ T cells (p<0.001) and reduced percentage of Gata-3+ (Th2) activated CD69+CD4+T cells (p<0.001) was detected in the mesenteric lymph nodes (MLN) of mice receiving scGOS/lcFOS/pAOS compared to control mice. Although no difference in the number or percentage of Tregs (CD4+Foxp3+) could be determined after scGOS/lcFOS/pAOS intervention, the percentage of CXCR3 + /T-bet+ (Th1-Tregs) was significantly reduced (p<0.05) in mice receiving scGOS/lcFOS/pAOS as compared to mice receiving placebo diets. Moreover, although no absolute difference in suppressive capacity could be detected, an alteration in cytokine profile suggests a regulatory T cell shift towards a reducing Th1 suppression profile, supporting an improved vaccination response.In conclusionThese data are indicative for improved vaccine responsiveness due to reduced Th1 suppressive capacity in the Treg population of mice fed the oligosaccharide specific diet, showing compartmentalization within the Treg population. The modulation of Tregs to control immune responses provides an additional arm of intervention using alternative strategies possibly leading to the development of improved vaccines.
Highlights
The induction of proper immune responsiveness to vaccinations shortly after birth or in immune compromised individuals is challenging
In mice receiving scGOS/long-chain fructooligosaccharides (lcFOS)/pectin hydrolysate derived acidic-oligosaccharides (pAOS), influenza vaccination results significantly (p0.001) increased influenzaspecific DTH responses compared to mice receiving placebo diets (Figure 1) which are comparable with earlier described immune modulation capacities of orally supplied oligosaccharides [22]
The percentage of Tregs were significantly lower (p0.05) in the mesenteric lymph nodes (MLN) of mice receiving scGOS/lcFOS/pAOS compared to mice receiving placebo diets (2.99 ± 0.53 placebo vs 1.06 ± 0.11 scGOS/lcFOS/pAOS % of Tregs) (Figure 4C)
Summary
The induction of proper immune responsiveness to vaccinations shortly after birth or in immune compromised individuals is challenging. The signaling within the intestine through pathogen recognition receptors like the toll like receptor (TLR) family for instance is crucial for the generation of effective immunity. Illustrative for this is that TLR2 influences the function of Tregs [5] and establishes a direct link between the intestinal microbiota and the control of immune responses through Tregs [6]. Tregs are important cells involved in immune regulation and play an increasing role in many immune related disorders of which many are found to be related to disturbed Treg function.
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