One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3 Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype, Co-receptor Expression and Innate Immune Responses in Healthy Elderly Subjects: Results From the United Kingdom Arm of the NU-AGE Trial

Monica Maijo, Kamal Ivory, Sarah J Clements, Jack R Dainty, Amy Jennings, Rachel Gillings, Susan Fairweather-Tait, Massimo Gulisano, Aurelia Santoro, Claudio Franceschi, Simon R Carding, Claudio Nicoletti, Monica Maijo, Kamal Ivory, Sarah J Clements, Jack R Dainty, Amy Jennings, Rachel Gillings, Susan Fairweather-Tait, Massimo Gulisano, Aurelia Santoro, Claudio Franceschi, Simon R Carding, Claudio Nicoletti

Abstract

Amongst the major features of aging are chronic low grade inflammation and a decline in immune function. The Mediterranean diet (MedDiet) is considered to be a valuable tool to improve health status, and although beneficial effects have been reported, to date, immunological outcomes have not been extensively studied. We aimed to test the hypothesis that 1 year of a tailored intervention based on the MedDiet with vitamin D (10 μg/day) would improve innate immune responses in healthy elderly subjects (65-79 years) from the English cohort (272 subjects recruited) of the NU-AGE randomized, controlled study (clinicaltrials.gov, NCT01754012). Of the 272 subjects forming the United Kingdom cohort a subgroup of 122 subjects (61 in the intervention group and 61 in the control group) was used to evaluate ex vivo innate immune response, phenotype of circulating immune cells, and levels of pro- and anti-inflammatory markers. Odds Ratio (OR) was calculated for all the parameters analyzed. After adjustment by gender, MedDiet-females with a BMI < 31 kg/m2 had a significant upregulation of circulating CD40+CD86+ cells (OR 3.44, 95% CI 1.01-11.75, P = 0.0437). Furthermore, in all MedDiet subjects, regardless of gender, we observed a MedDiet-dependent changes, although not statistically significant of immune-critical parameters including T cell degranulation, cytokine production and co-receptor expression. Overall, our study showed that adherence to an individually tailored Mediterranean-like dietary pattern with a daily low dose of vitamin D3 supplements for 1 year modified a large variety of parameters of immune function in healthy, elderly subjects. We interpreted these data as showing that the MedDiet in later life could improve aspects of innate immunity and thus it could aid the design of strategies to counteract age-associated disturbances. Clinical Trial Registration: clinicaltrials.gov, NCT01754012.

Keywords: NU-AGE; aging; dietary intervention; elderly; inflammation; nutrition.

Figures

FIGURE 1
FIGURE 1
Flow chart summarizing recruitment and retention of study participants. 272 volunteers were recruited at baseline in the NU-AGE English (Norwich) cohort (134 control, 138 MedDiet) for the dietary intervention. This study (blue boxes) focuses on the effects of dietary intervention on a variety of parameters of the immune responses.
FIGURE 2
FIGURE 2
Effects of MedDiet on CD40+CD86+ expression following in vitro challenge with TLR agonists. PBMC were cultured with a cocktail of TLRs agonists (PolyA:U, Imiquimod, ODN-M362, LPS, Pam2CSK4) for 22 h. Forest plot of the study of the CD40+CD86+ lymphocytes comparing the association between Mediterranean diet and normal diet after 1 year of intervention with the random effect model. Associations were investigated based on an adjusted Mantel–Haenszel odds ratio (OR), stratified by gender (A) or BMI > 31 kg/m2(B). OR and 95%Cl were calculated. Cl, confidence interval.
FIGURE 3
FIGURE 3
Effects of the MedDiet on cytokine expression following in vitro challenge with TLR agonists-all individual values. PBMC were cultured with a cocktail of TLRs agonists (PolyA:U, Imiquimod, ODN-M362, LPS, Pam2CSK4) for 22 h. Levels of cytokines were determined in culture supernatants. Representation of the individual values for IFN-β (A), IL-12p40/70 ratio (B), SOCS3 (C) and IL-12Rβ1 (D) concentration in all the volunteers at baseline and after 1 year of intervention. Results showed a tendency toward increased production of IFN-β (OR 1.98, 95%CI 0.86–4.53, P = 0.1056), and decreased production of IL-12Rβ1 (OR 0.50, 95%CI 0.22–1.13, P = 0.0929), SOCS3 (OR 0.50, 95%CI 0.21–1.18, P = 0.1108) and the ratio between IL-12p40/IL-12p70 (OR 0.54, 95%CI 0.26–1.16, P = 0.1122. OR = odds ratio), CI, confidence intervals.
FIGURE 4
FIGURE 4
Cytokine expression following in vitro challenge with TLR agonists- Changes (Δ) of the parameter values in MedDiet and control diet at baseline and after 1-year of intervention. Δ of the parameters at baseline (T0) and after 1-year (T1) for IFN-β (A), IL-12p40/70 ratio (B), SOCS3 (C), and IL-12Rβ1 (D) concentration were calculated and compared. For each parameter, the mean ± SD of the Δ at T0 and T1 for the control group and MedDiet group is shown in the relevant inset.
FIGURE 5
FIGURE 5
Effects of MedDiet on dendritic cell (DC) subpopulations. Whole blood was used at baseline and at the end of the 1-year dietary intervention to determine myeloid (m)DC and plasmacytoid (p)DC ratio. Representation of the gating strategy for the DCs enumeration is shown in (A–C). (D) Boxplot showing the difference in the control and diet groups for mDC/pDC ratio right panel. A decrease, but not statistically significant of the ratio of mDC/pDC (P = 0.0536) was observed.
FIGURE 6
FIGURE 6
Expression of co-stimulatory molecules on freshly isolated PBMC. PBMCs were stained with CD3 and CD28 antibodies. All individual values for both the MedDiet and control group at T0 and T1 are shown (A). A trend toward higher frequency of CD3+CD28+ cells in the MedDiet intervention group was seen in both genders (OR 2.19, 95%CI 0.92–5.21, P = 0.1174). Also, changes (Δ) of parameter values in MedDiet and control diet at baseline and after 1-year of intervention were determined (mean ± SD in inset) and compared (B).

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