title: Malnutrition in Healthy Individuals Results in Increased Mixed Cytokine Profiles, Altered Neutrophil Subsets and Function.
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.
authors.affiliation: Department of Medicine, Imperial College London, London, United Kingdom.|Leishmaniasis Research and Treatment Centre, Gondar University, Gondar, Ethiopia.
authors.forename: Y
authors.initials: Y
authors.lastname: Takele
authors.affiliation: Department of Immunology, University of Gondar, Gondar, Ethiopia.
authors.forename: E
authors.initials: E
authors.lastname: Adem
authors.affiliation: Department of Immunology, University of Gondar, Gondar, Ethiopia.
authors.forename: M
authors.initials: M
authors.lastname: Getahun
authors.affiliation: Department of Immunology, University of Gondar, Gondar, Ethiopia.
authors.forename: F
authors.initials: F
authors.lastname: Tajebe
authors.affiliation: Department of Immunology, University of Gondar, Gondar, Ethiopia.
authors.forename: A
authors.initials: A
authors.lastname: Kiflie
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: A
authors.initials: A
authors.lastname: Hailu
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Raynes
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University, Gondar, Ethiopia.
authors.forename: B
authors.initials: B
authors.lastname: Mengesha
authors.affiliation: Department of Epidemiology and Biostatistics, University of Gondar, Gondar, Ethiopia.
authors.forename: T A
authors.initials: TA
authors.lastname: Ayele
authors.affiliation: Department of Mathematics and Statistics, University of Hasselt, Hasselt, Belgium.
authors.forename: Z
authors.initials: Z
authors.lastname: Shkedy
authors.affiliation: Department of Immunology, University of Gondar, Gondar, Ethiopia.
authors.forename: M
authors.initials: M
authors.lastname: Lemma
authors.affiliation: Department of Internal Medicine, University of Gondar, Gondar, Ethiopia.
authors.forename: E
authors.initials: E
authors.lastname: Diro
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Toulza
authors.affiliation: Department of Cellular Immunology, Max-Planck-Institute for Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Modolell
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Centre Mainz, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Munder
authors.affiliation: Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: I
authors.initials: I
authors.lastname: Müller
authors.affiliation: Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Kropf
mesh_terms: D000328:Adult; D001119:Arginase / Q000235:genetics / Q000276:immunology; D015992:Body Mass Index; D016516:CD4-CD8 Ratio; D019070:Cell Lineage / Q000276:immunology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility; D005002:Ethiopia; D005260:Female; D015870:Gene Expression; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D044342:Malnutrition / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D009894:Opportunistic Infections / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D001119:Arginase