Levels of Th2 cytokines in plasma.

<p>The plasma from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) was tested by Luminex for the levels of IL-4, IL-5 and IL-13. Fig 2A, C and E show correlations between BMI and the different cytokines and statistical significance was established using a Spearman rank test. Fig B, D and F show cytokine levels between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p

NDGs' effector functions.

<p>NDGs' effector functions.</p

CD3ζ expression in CD4⁺ and CD8⁺ T cells in individuals with normal and low BMI.

<p>CD3ζ expression in CD4⁺ and CD8⁺ T cells in individuals with normal and low BMI.</p

ROS production.

<p>NDGs from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) were isolated by double density gradient centrifugation NDGs and the capacity of NDGs to produce ROS was assessed by flow cytometry. Fig 7A and C show correlations between BMI and ROS production and statistical significance was established using a Spearman rank test. Fig 7B and D show ROS production between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p

Haematological profile and percentages and ratio of CD4⁺ and CD8⁺ T cells of individuals with normal and low BMI.

<p>Haematological profile and percentages and ratio of CD4⁺ and CD8⁺ T cells of individuals with normal and low BMI.</p

Malnutrition in Healthy Individuals Results in Increased Mixed Cytokine Profiles, Altered Neutrophil Subsets and Function

<div><p>Malnutrition is commonly associated with increased infectious disease susceptibility and severity. Whereas malnutrition might enhance the incidence of disease as well as its severity, active infection can in turn exacerbate malnutrition. Therefore, in a malnourished individual suffering from a severe infection, it is not possible to determine the contribution of the pre-existing malnutrition and/or the infection itself to increased disease severity. In the current study we focussed on two groups of malnourished, but otherwise healthy individuals: moderately malnourished (BMI: 18.4–16.5) and severely malnourished (BMI <16.5) and compared several immune parameters with those of individuals with a normal BMI (≥18.5). Our results show a similar haematological profile in all three groups, as well as a similar ratio of CD4⁺ and CD8⁺ T cells. We found significant correlations between low BMI and increased levels of T helper (Th) 1 (Interferon (IFN)-γ, (interleukin (IL)-2, IL-12), Th2 (IL-4, IL-5, IL-13), as well as IL-10, IL-33 and tumor necrosis factor-α, but not IL-8 or C reactive protein. The activities of arginase, an enzyme associated with immunosuppression, were similar in plasma, peripheral blood mononuclear cells (PBMC) and neutrophils from all groups and no differences in the expression levels of CD3ζ, a marker of T cell activation, were observed in CD4⁺ and CD8⁺T cells. Furthermore, whereas the capacity of neutrophils from the malnourished groups to phagocytose particles was not impaired, their capacity to produce reactive oxygen species was impaired. Finally we evaluated the frequency of a subpopulation of low-density neutrophils and show that they are significantly increased in the malnourished individuals. These differences were more pronounced in the severely malnourished group. In summary, our results show that even in the absence of apparent infections, healthy malnourished individuals display dysfunctional immune responses that might contribute to increased susceptibility and severity to infectious diseases.</p></div

TNF-α.

<p>The plasma from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) was tested by ELISA for the levels of IL-8. Fig 4A shows correlations between BMI and TNF-α levels and statistical significance was established using a Spearman rank test. Fig 4B shows TNF-α levels between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p

IL-10 and IL-33 levels in plasma.

<p>The plasma from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) was tested by Luminex for the levels of IL-10 and IL-33. Fig 3A, C and E show correlations between BMI and the different cytokines and statistical significance was established using a Spearman rank test. Fig 3B, D and F show cytokine levels between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p

Arginase activity in plasma, PBMCs and neutrophils of individuals with normal and low BMI.

<p>Arginase activity in plasma, PBMCs and neutrophils of individuals with normal and low BMI.</p

Frequency of LDGs in PBMCs.

<p>PBMCs from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) were isolated by density gradient centrifugation and the frequency of LDGs (CD15+arginase+ cells) was determined by flow cytometry. Fig 5A shows the correlation between BMI and the frequency of LDGs and statistical significance was established using a Spearman rank test. Fig 5B shows the frequency of LDGs between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p