Abstract
Obesity is associated with alterations in functionality of immune cells, like macrophages and natural killer (NK) cells, leading to an increased risk for severe infections and several cancer types. This study aimed to examine immune cell populations and functional NK cell parameters focusing on NK cell subset phenotypes in normal-weight and obese humans. Therefore, peripheral blood mononuclear cells (PBMCs) were isolated from normal-weight and obese individuals and analyzed by flow cytometry. Results show no significant changes in the frequency of monocytes, B lymphocytes, or NKT cells but a significantly increased frequency of T lymphocytes in obesity. The frequency of total NK cells was unaltered, whereas the number of low cytotoxic CD56bright NK cell subset was increased, and the number of high cytotoxic CD56dim NK cell subset was decreased in obese subjects. In addition, the frequency of CD56bright NK cells expressing the activating NK cell receptor NKG2D as well as intracellular interferon (IFN)-γ was elevated in the obese study group. In contrast, the frequency of NKG2D- and IFN-γ-positive CD56dim NK cells was lower in obesity compared to normal-weight individuals. Moreover, the expression of the activation marker CD69 was decreased in NK cells, which can be attributed to a reduction of CD69-positive CD56dim NK cells in obese subjects. In conclusion, data reveal an impaired NK cell phenotype and NK cell subset alterations in obese individuals. This NK cell dysfunction might be one link to the higher cancer risk and the elevated susceptibility for viral infections in obesity.
Highlights
The rising prevalence of overweight and obesity has become a major global health challenge as excess body weight is associated with nearly 4 million deaths and 120 million disabilityadjusted life-years [1]
Obese individuals showed a significantly higher body weight and body mass index (BMI) compared to the normal-weight study group (Table 1)
Results showed significantly higher plasma leptin concentrations in obese individuals compared to normal-weight subjects (Table 2)
Summary
The rising prevalence of overweight and obesity has become a major global health challenge as excess body weight is associated with nearly 4 million deaths and 120 million disabilityadjusted life-years [1]. Obesity is associated with metaflammation, a state of a systemic chronic low-grade inflammation, associated with dysfunctions of several immune cells, like B lymphocytes, T lymphocytes, and macrophages [10,11,12]. Previous studies demonstrated an impaired functionality of natural killer (NK) cells in the state of obesity [13,14,15,16,17]. Natural killer cells express both activating and inhibitory receptors that are involved in regulating NK cell effector functions. NK cells secrete several cytokines, like tumor necrosis factor (TNF)-α and interferon (IFN)-γ, in order to regulate the adaptive immune response [18]
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