scholarly journals Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

2019 ◽  
Vol 7 (1) ◽  
pp. e000751 ◽  
Author(s):  
Lisa Willemsen ◽  
Annette E Neele ◽  
Saskia van der Velden ◽  
Koen H M Prange ◽  
Myrthe den Toom ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Cell Function ◽  
Immune Cell ◽  
Peritoneal Macrophages ◽  
Macrophage Phenotype ◽  
Adipose Tissue Macrophages ◽  
Microbial Infections ◽  
Impaired Immune Response

IntroductionObesity is recognized as a risk factor for various microbial infections. The immune system, which is affected by obesity, plays an important role in the pathophysiology of these infections and other obesity-related comorbidities. Weight loss is considered the most obvious treatment for obesity. However, multiple studies suggest that the comorbidities of obesity may persist after weight loss. Deregulation of immune cells including adipose tissue macrophages of obese individuals has been extensively studied, but how obesity and subsequent weight loss affect immune cell function outside adipose tissue is not well defined.Research design and methodsHere we investigated the phenotype of non-adipose tissue macrophages by transcriptional characterization of thioglycollate-elicited peritoneal macrophages (PM) from mice with diet-induced obesity and type 2 diabetes (T2D). Subsequently, we defined the characteristics of PMs after weight loss and mimicked a bacterial infection by exposing PMs to lipopolysaccharide.Results and conclusionsIn contrast to the proinflammatory phenotype of adipose tissue macrophages in obesity and T2D, we found a deactivated state of PMs in obesity and T2D. Weight loss could reverse this deactivated macrophage phenotype. Anti-inflammatory characteristics of these non-adipose macrophages may explain why patients with obesity and T2D have an impaired immune response against pathogens. Our data also suggest that losing weight restores macrophage function and thus contributes to the reduction of immune-related comorbidities in patients.

scholarly journals HIF1α activation in dendritic cells under sterile conditions promotes an anti-inflammatory phenotype through accumulation of intracellular lipids

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Elizabeth G. Wood ◽  
Claire E. Macdougall ◽  
Hazel Blythe ◽  
Marc Clément ◽  
Romain A. Colas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cell Function ◽  
Immune Cell ◽  
Lipid Synthesis ◽  
Mortality And Morbidity ◽  
Intracellular Lipids ◽  
Adipose Tissue Dysfunction ◽  
Disease Mortality ◽  
Key Factor ◽  
Inflammatory Phenotype

AbstractObesity is among the leading causes of elevated cardiovascular disease mortality and morbidity. Adipose tissue dysfunction, insulin resistance and inflammation are recognized as important risk factors for the development of cardiovascular disorders in obesity. Hypoxia appears to be a key factor in adipose tissue dysfunction affecting not only adipocytes but also immune cell function. Here we examined the effect of hypoxia-induced transcription factor HIF1α activation on classical dendritic cell (cDCs) function during obesity. We found that deletion of Hif1α on cDCs results in enhanced adipose-tissue inflammation and atherosclerotic plaque formation in a mouse model of obesity. This effect is mediated by HIF1α-mediated increased lipid synthesis, accumulation of lipid droplets and alter synthesis of lipid mediators. Our findings demonstrate that HIF1α activation in cDCs is necessary to control vessel wall inflammation.

scholarly journals Do high-salt microenvironments drive hypertensive inflammation?

2017 ◽  
Vol 312 (1) ◽  
pp. R1-R4 ◽  
Author(s):  
Jason D. Foss ◽  
Annet Kirabo ◽  
David G. Harrison
Keyword(s):  
Skeletal Muscle ◽  
Immune Response ◽  
Cell Function ◽  
Immune Cell ◽  
Vascular Inflammation ◽  
Immune Cell Function ◽  
Dietary Salt ◽  
Salt Accumulation ◽  
Human Hypertension ◽  
Global Epidemic

Hypertension is a global epidemic affecting over one billion people worldwide. Despite this, the etiology of most cases of human hypertension remains obscure, and treatment remains suboptimal. Excessive dietary salt and inflammation are known contributors to the pathogenesis of this disease. Recently, it has been recognized that salt can accumulate in the skin and skeletal muscle, producing concentrations of sodium greater than the plasma in hypertensive animals and humans. Such elevated levels of sodium have been shown to alter immune cell function. Here, we propose a model in which tissue salt accumulation causes an immune response leading to renal and vascular inflammation and hypertension.

scholarly journals Impact of weight loss and partial weight regain on immune cell and inflammatory markers in adipose tissue in male mice

2020 ◽  
Vol 129 (4) ◽  
pp. 909-919
Author(s):  
Alexander T. Sougiannis ◽  
Brandon N. VanderVeen ◽  
Taryn L. Cranford ◽  
Reilly T. Enos ◽  
Kandy T. Velazquez ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Immune Cells ◽  
High Fat Diet ◽  
Inflammatory Markers ◽  
Weight Regain ◽  
Immune Cell ◽  
High Fat ◽  
Inflammatory Status ◽  
Partial Weight

We examined the immune and inflammatory status of adipose tissue in mice after they underwent weight loss followed by partial weight regain. We show an increase in selected immune cells and inflammatory mediators, in high-fat diet-fed mice that had prior exposure to a high-fat diet. Although weight fluctuations appear to exacerbate immune cell abundance and inflammation in adipose tissue, severity is less than in mice that were exposed to sustained high-fat diet feedings.

scholarly journals Hypoxia/HIF Modulates Immune Responses

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Yuling Chen ◽  
Timo Gaber
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Oxygen Availability ◽  
The Body ◽  
Low Oxygen ◽  
Adaptive Immune

Oxygen availability varies throughout the human body in health and disease. Under physiological conditions, oxygen availability drops from the lungs over the blood stream towards the different tissues into the cells and the mitochondrial cavities leading to physiological low oxygen conditions or physiological hypoxia in all organs including primary lymphoid organs. Moreover, immune cells travel throughout the body searching for damaged cells and foreign antigens facing a variety of oxygen levels. Consequently, physiological hypoxia impacts immune cell function finally controlling innate and adaptive immune response mainly by transcriptional regulation via hypoxia-inducible factors (HIFs). Under pathophysiological conditions such as found in inflammation, injury, infection, ischemia and cancer, severe hypoxia can alter immune cells leading to dysfunctional immune response finally leading to tissue damage, cancer progression and autoimmunity. Here we summarize the effects of physiological and pathophysiological hypoxia on innate and adaptive immune activity, we provide an overview on the control of immune response by cellular hypoxia-induced pathways with focus on the role of HIFs and discuss the opportunity to target hypoxia-sensitive pathways for the treatment of cancer and autoimmunity.

scholarly journals Inhibition of PI3K Isoform p110γ Increases both Anti-Tumor and Immunosuppressive Responses to Aggressive Murine Head and Neck Squamous Cell Carcinoma with Low Immunogenicity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 953
Author(s):  
Kelvin Anderson ◽  
Nathan Ryan ◽  
Anastasia Alkhimovitch ◽  
Arham Siddiqui ◽  
Steve Oghumu
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Pi3k Pathway ◽  
Wild Type ◽  
Orthotopic Mouse Model ◽  
Tumor Bearing

HNSCC is the sixth most common cancer, with around 650,000 new cases yearly. Gain of function mutations in the PI3K pathway are common in HNSCC, and inhibition of the PI3K p110γ subunit has shown promise in HNSCC treatment. However, given that PI3K p110γ plays an important role in myeloid and lymphoid immune cell function, it is essential to understand how PI3K p110γ inhibition affects the anti-tumor immune response independent of tumor cells. To elucidate PI3K p110γ function in HNSCC, we employed an orthotopic mouse model using poorly immunogenic and aggressive cell line MOC2 on Pik3cg-/-mice. We observed that wild-type and Pik3cg-/-mice displayed similar rates of HNSCC tumor growth and metastasis after 20 days following tumor injection. T-cell infiltration and intrinsic T-cell responses to MOC2 oral tumors were comparable between wild-type and Pik3cg-/-mice. Interestingly, the immune response of tumor-bearing Pik3cg-/- mice was marked by increased anti-tumor cytotoxic molecules (IFN-γ, IL-17)) by T-cells and immune checkpoint marker (PD-L1, PD-1) expression by myeloid cells and T-cells compared to tumor-bearing wild-type mice. Taken together, our findings demonstrate that inhibition of PI3K p110γ modulates tumor-associated immune cells, which likely potentiates HNSCC treatment when used in combination with selective checkpoint inhibitors.

scholarly journals Time-Restricted Feeding Restores Obesity-Induced Alteration in Adipose Tissue Immune Cell Phenotype

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3780
Author(s):  
Youngyoon Lee ◽  
Yelim Kim ◽  
Minam Lee ◽  
Dayong Wu ◽  
Munkyong Pae
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
High Fat Diet ◽  
Immune Cell ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Restricted Feeding ◽  
High Fat ◽  
Low Fat Diet ◽  
Adipose Tissue Macrophages

Studies suggest that time-restricted feeding (TRF) may prevent obesity and its commodities. At present, little is known about how TRF impacts immune cells, and whether such an effect is linked to altered metabolic parameters under condition of a high-fat diet (HFD)-induced obesity. To address these issues, we conducted a study in which we determined whether TRF has therapeutic efficacy against weight gain, adiposity, as well as associated immune cell disturbance found in obese mice. Six-week-old male C57BL/6 mice were fed a low-fat diet (LFD) or HFD ad libitum for six weeks, after which time a subgroup of HFD mice was switched to the 10 h TRF paradigm (HFD-TRF) for additional eight weeks. We found that TRF intervention reduced HFD-induced weight gain. Even with comparable fat mass and mean adipocyte area, the HFD-TRF group had lower mRNA levels of proinflammatory cytokine Tnfα and chemokine Ccl8, along with reduced numbers of adipose tissue macrophages (ATM), CD11c+ ATM, and CD8+ T cell compared to the HFD group, while maintaining CD8+ to CD4+ ratio at levels similar to those in the LFD group. Furthermore, TRF intervention was effective in improving glucose tolerance and reducing HOMA-IR. Taken together, our findings suggest that TRF restores the obesity-induced alteration in immune cell composition, and this effect may in part contribute to health benefits (including insulin sensitivity) of practicing TRF.

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