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

Y Takele,T A Ayele,B Mengesha,M Munder,J Raynes,M Lemma,M Getahun,F Tajebe,F Toulza,I Müller,P Kropf,A Hailu,E Adem,Z Shkedy,E Diro,A Kiflie,M Modolell,Rasheed Ahmad

doi:10.1371/journal.pone.0157919

Abstract

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.

Highlights

Undernutrition, here referred to as malnutrition, is a result of inadequate diet and/or malabsorption of nutrients
We first assessed the haematological profile of our cohort and as shown in Table 2, no significant differences (p>0.05) were observed in white blood cells (WBC), neutrophils, lymphocytes, red blood cell (RBC), haemoglobin (Hgb) and platelet counts between individuals with a WBC Neutrophils Lymphocytes RBC
And 6, no significant differences were observed in all the parameters measured. These results show that arginase activity in plasma, PBMCs and normal density granulocytes (NDGs), as well as the levels of degranulation markers on NDGs and low-density granulocytes (LDGs) we assessed are similar on all groups; malnourished individuals have significantly more LDGs in their PBMCs

Summary

Introduction

Undernutrition, here referred to as malnutrition, is a result of inadequate diet and/or malabsorption of nutrients. Protein energy malnutrition (PEM) has been associated with different infectious diseases including malaria, tuberculosis, lower respiratory tract infections and diarrheal diseases; and these are the major cause of morbidity and mortality in developing countries [2, 3][4, 5]. Malnutrition is thought to be one of the major causes of immunodeficiency: in malnourished patients, both innate and acquired immunity are affected [6, 7]. It has been shown that malnutrition and the subsequent impaired immune responses reduce the efficacy of oral vaccines in developing countries [16]

Objectives

Methods

Results

Conclusion