Perturbation of the Monocyte Compartment in Human Obesity

Friedrich, Kathleen; Sommer, Miriam; Strobel, Sarah; Thrum, Stephan; Blüher, Matthias; Wagner, Ulf; Rossol, Manuela

doi:10.3389/fimmu.2019.01874

Cited by 76 publications

(83 citation statements)

References 46 publications

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“…One interesting finding of this study was the negative correlation between the BMI and frequency of peripheral blood monocytes. This is in contrast to previous reports of a positive association between CD56+ monocytes and body fat, body mass index, waist circumference, C-reactive protein, triglycerides, and HbA1c in obese individuals [ 71 ]. A possible explanation for observed discrepancies is that the BMI of our participants was in the range for normal weight.…”

Section: Discussioncontrasting

confidence: 99%

Leukocyte Activation and Antioxidative Defense Are Interrelated and Moderately Modified by n-3 Polyunsaturated Fatty Acid-Enriched Eggs Consumption—Double-Blind Controlled Randomized Clinical Study

et al. 2020

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This placebo-controlled, double-blind, randomized, interventional study investigated the effects of low/intermediate doses of n-3 polyunsaturated fatty acids (PUFAs) on the endothelial function, markers of leukocyte activation, and oxidative status following dietary intake of n-3 PUFA-enriched hen eggs in young healthy individuals. Twenty young healthy adults of both sexes who consumed n-3 PUFA-enriched hen eggs (two eggs per day, for three weeks, total of approximately 407 mg/day n-3 PUFAs) or regular eggs (two eggs per day for three weeks, total of approximately 75 mg/day n-3 PUFAs) participated in this study. Skin microvascular endothelium-independent and endothelium-dependent vasodilation were assessed by laser Doppler flowmetry. Serum lipid profile and content of free fatty acids, markers of leukocyte activation, biochemical parameters of oxidative stress, as well as antioxidative enzymes serum activity were measured before and after respective dietary protocol. The results of this study revealed significant differences in the markers of leukocyte activation (such as CD11a/LFA-1) and antioxidative defense, which are related to increased intake of n-3 PUFAs, providing the evidence that consumption of nutritionally enriched hen eggs may affect physiological processes related to oxidative balance. The absence of significant changes in microvascular reactivity following supplementation with a low-intermediate dose of n-3 PUFAs, unlike in our previous studies where functional eggs contained ~1 g of n-3 PUFA, suggests the existence of a dose-dependent effect.

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Section: Discussioncontrasting

confidence: 99%

Leukocyte Activation and Antioxidative Defense Are Interrelated and Moderately Modified by n-3 Polyunsaturated Fatty Acid-Enriched Eggs Consumption—Double-Blind Controlled Randomized Clinical Study

et al. 2020

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“…Metabolic disease and obesity is associated with chronic, low grade inflammation and is associated with differences in monocyte subsets (Friedrich et al, 2019;Figueroa-Vega et al, 2020). While all CD14 + CD16 + (classical monocytes), CD14 dim CD16 + (intermediate) and CD14 − CD16 ++ (nonclassical) monocytes are susceptible to infection by the DENV, the non-classical monocytes are the main produced of inflammatory cytokines and IL-10, which are implicated in SD (Wong et al, 2012).…”

Section: Metabolic Disease and Innate Immunitymentioning

confidence: 99%

“…IFITI and CD163 expression in CD14+CD16+ monocytes, was shown to precede the development of severe dengue (Zanini et al, 2018). As those with metabolic disease and obesity have a higher frequency of the non-classical types of monocytes (Friedrich et al, 2019), increased infection of this subtype by the DENV in such individuals could lead to severe dengue. Increase in mast cell numbers are also seen in adipose tissues of obese individuals, which are thought to contribute to low grade inflammation associated with metabolic syndrome and obesity (Elieh Ali Komi et al, 2020).…”

Section: Metabolic Disease and Innate Immunitymentioning

confidence: 99%

Dysfunctional Innate Immune Responses and Severe Dengue

Malavige

Jeewandara

Ogg

2020

Front. Cell. Infect. Microbiol.

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Although infection with the dengue virus (DENV) causes severe dengue, it causes a mild self-limiting illness in the majority of individuals. There is emerging evidence that an aberrant immune response in the initial stages of infection lead to severe disease. Many inflammatory cytokines, chemokines, and lipid mediators are significantly higher in patients with severe dengue compared to those who develop mild infection, during febrile phase of illness. Monocytes, mast cells, and many other cells of the immune system, when infected with the DENV, especially in the presence of poorly neutralizing antibodies, leads to production of pro-inflammatory cytokines and inhibition of interferon signaling pathways. In addition, production of immunosuppressive cytokines such as IL-10 further leads to inhibition of cellular antiviral responses. This dysregulated and aberrant immune response leads to reduced clearance of the virus, and severe dengue by inducing a vascular leak and excessive inflammation due to high levels of inflammatory cytokines. Individuals with comorbid illnesses could be prone to more severe dengue due to low grade endotoxemia, gut microbial dysbiosis and an altered phenotype of innate immune cells. The immunosuppressive and inflammatory lipid mediators and altered phenotype of monocytes are likely to further act on T cells and B cells leading to an impaired adaptive immune response to the virus. Therefore, in order to identify therapeutic targets for treatment of dengue, it would be important to further characterize these mechanisms in order for early intervention. In this review, we discuss the differences in the innate immune responses in those who progress to develop severe dengue, compared to those with milder disease in order to understand the mechanisms that lead to severe dengue.

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“…Although these adaptations meet the need for more innate immune cells, this lymphoid-myeloid switch and the enhanced myelopoiesis might also perpetuate inflammatory and metabolic disorders by generating a feed-forward loop between inflammation-triggered MP cells and the inflamed tissue. 4 Alterations in MPs, as well as the expansion of pro-inflammatory monocytes and MDSCs, also arise in high-fat diet (HFD)-induced obesity 34 – 36 and are considered a biomarker for the risk of obesity-associated diseases, such as diabetes and atherosclerosis. 37 , 38 Notably, it has been hypothesized that one of the mechanisms by which obesity promotes cancer mortality is through the induction of MDSCs.…”

Section: Interconnection Between Metabolic Syndrome and Inflammationmentioning

confidence: 99%

Implications of metabolism-driven myeloid dysfunctions in cancer therapy

et al. 2020

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Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid responses. In chronic inflammatory states, including cancer, this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils, macrophages, and dendritic cells (DCs), thus giving rise to a decline in the antitumor effector lymphoid response. Cancer-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors, resulting in unresolved and chronic inflammation. This pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool, which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor site. Therefore, persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer, as well as to the severity of a broad range of diseases, including metabolic syndrome and autoimmune and infectious diseases. The aims of this review are to (1) define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients, (2) discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes, and (3) explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor immunity. We propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects (irAEs) for current therapeutic strategies, including immune checkpoint inhibitor (ICI) therapy.

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Perturbation of the Monocyte Compartment in Human Obesity

Cited by 76 publications

References 46 publications

Leukocyte Activation and Antioxidative Defense Are Interrelated and Moderately Modified by n-3 Polyunsaturated Fatty Acid-Enriched Eggs Consumption—Double-Blind Controlled Randomized Clinical Study

Leukocyte Activation and Antioxidative Defense Are Interrelated and Moderately Modified by n-3 Polyunsaturated Fatty Acid-Enriched Eggs Consumption—Double-Blind Controlled Randomized Clinical Study

Dysfunctional Innate Immune Responses and Severe Dengue

Implications of metabolism-driven myeloid dysfunctions in cancer therapy

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