scholarly journals Implications of Inflammatory States on Dysfunctional Immune Responses in Aging and Obesity

2021 ◽  
Vol 2 ◽  
Author(s):  
Alyssa L. Thomas ◽  
Pablo C. Alarcon ◽  
Senad Divanovic ◽  
Claire A. Chougnet ◽  
David A. Hildeman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Immune Cell ◽  
Accelerated Aging ◽  
Clinical Problem ◽  
Cell Types ◽  
Low Grade ◽  
Potential Contribution ◽  
Altered State ◽  
Low Grade Inflammation

Aging and obesity are two conditions characterized by chronic, low-grade inflammation. While both conditions are also associated with dysfunctional immune responses, the shared and distinct underlying mechanisms are just starting to be uncovered. In fact, recent findings have suggested that the effects of obesity on the immune system can be thought of as a state of accelerated aging. Here we propose that chronic, low-grade inflammation seen in obesity and aging is complex, affects multiple cell types, and results in an altered basal immune state. In aging, part of this altered state is the emergence of regulatory immune populations that lead to further immune dysfunction in an attempt to reduce chronic inflammation. While in obesity, part of the altered state is the effect of expanding adipose tissue on immune cell function. Thus, in this review, we compare, and contrast altered immune states in aging and obesity and discuss their potential contribution to a shared clinical problem- decreased vaccine responsiveness.

scholarly journals The Potential Effects of Probiotics and ω-3 Fatty Acids on Chronic Low-Grade Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2402 ◽  
Author(s):  
Ashley N. Hutchinson ◽  
Lina Tingö ◽  
Robert Jan Brummer
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Cell Function ◽  
Immune Cell ◽  
Low Grade ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Immune Mediators ◽  
Low Grade Inflammation ◽  
Microbiota Diversity

Chronic low-grade inflammation negatively impacts health and is associated with aging and obesity, among other health outcomes. A large number of immune mediators are present in the digestive tract and interact with gut bacteria to impact immune function. The gut microbiota itself is also an important initiator of inflammation, for example by releasing compounds such as lipopolysaccharides (LPS) that may influence cytokine production and immune cell function. Certain nutrients (e.g., probiotics, ω-3 fatty acids [FA]) may increase gut microbiota diversity and reduce inflammation. Lactobacilli and Bifidobacteria, among others, prevent gut hyperpermeability and lower LPS-dependent chronic low-grade inflammation. Furthermore, ω-3 FA generate positive effects on inflammation-related conditions (e.g., hypertriglyceridemia, diabetes) by interacting with immune, metabolic, and inflammatory pathways. Ω-3 FA also increase LPS-suppressing bacteria (i.e., Bifidobacteria) and decrease LPS-producing bacteria (i.e., Enterobacteria). Additionally, ω-3 FA appear to promote short-chain FA production. Therefore, combining probiotics with ω-3 FA presents a promising strategy to promote beneficial immune regulation via the gut microbiota, with potential beneficial effects on conditions of inflammatory origin, as commonly experienced by aged and obese individuals, as well as improvements in gut-brain-axis communication.

scholarly journals Prostaglandin E2 Signaling Mediates Oenocytoid Immune Cell Function and Lysis, Limiting Bacteria and Plasmodium Oocyst Survival in Anopheles gambiae

2021 ◽  
Vol 12 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith
Keyword(s):  
Immune Responses ◽  
Prostaglandin E2 ◽  
Anopheles Gambiae ◽  
Cell Function ◽  
Immune Cell ◽  
Protective Effects ◽  
Immune Cell Function ◽  
Humoral Immune ◽  
High Concentrations ◽  
Prostaglandin E2 Receptor

Lipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet in arthropods of medical importance, studies have been limited. Here, we describe a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and demonstrate that its expression is most abundant in oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing, we demonstrate that prostaglandin E2 signaling regulates a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs) that are strongly expressed in populations of oenocytoids. We demonstrate that PGE2 signaling via the AgPGE2R significantly limits both bacterial replication and Plasmodium oocyst survival. Additional experiments establish that PGE2 treatment increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, genes essential to anti-Plasmodium immune responses that promote oocyst killing. We also provide evidence that the mechanisms of PGE2 signaling are concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of lower concentrations of PGE2 on anti-Plasmodium immunity. Taken together, our results provide new insights into the role of PGE2 signaling on immune cell function and its contributions to mosquito innate immunity that promote pathogen killing.

scholarly journals Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Santopaolo ◽  
Niall Sullivan ◽  
Anita Coral Thomas ◽  
Valeria Vincenza Alvino ◽  
Lindsay B. Nicholson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
T Cells ◽  
Insulin Sensitivity ◽  
Adaptive Immunity ◽  
Cell Function ◽  
Immune Cell ◽  
Low Grade ◽  
Cardiac Damage

Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function.Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance.Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity.Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.

scholarly journals Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Kang ◽  
Marjan Nasr ◽  
Yiru Guo ◽  
Shizuka Uchida ◽  
Tyler Weirick ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Innate Immunity ◽  
Mechanism Of Action ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Mesenchymal Cell ◽  
Cell Types

Abstract Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration—suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably linked to wound healing/remodeling in the ischemically injured heart, the reparative actions of CMCs may be attributed to their immunoregulatory properties. The current study evaluated the consequences of CMC administration on post myocardial infarction (MI) immune responses in vivo and paracrine-mediated immune cell function in vitro. CMC administration preferentially elicited the recruitment of cell types associated with innate immunity (e.g., monocytes/macrophages and neutrophils). CMC paracrine signaling assays revealed enhancement in innate immune cell chemoattraction, survival, and phagocytosis, and diminished pro-inflammatory immune cell activation; data that identifies and catalogues fundamental immunomodulatory properties of CMCs, which have broad implications regarding the mechanism of action of CMCs in cardiac repair.

scholarly journals Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

2019 ◽  
Vol 44 (5) ◽  
pp. 512-520 ◽  
Author(s):  
Débora Romualdo Lacerda ◽  
Michele Macedo Moraes ◽  
Albená Nunes-Silva ◽  
Kátia Anunciação Costa ◽  
Débora Fernandes Rodrigues ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Aerobic Training ◽  
Immune Cell ◽  
Control Diet ◽  
Moderate Intensity ◽  
Low Grade ◽  
Carbohydrate Diet ◽  
Cytokine Levels ◽  
Low Grade Inflammation

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

scholarly journals Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hao Zhang ◽  
Fan Fan ◽  
Yuanqiang Yu ◽  
Zeyu Wang ◽  
Fangkun Liu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Malignant Gliomas ◽  
Leading Edge ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Lymphocyte Migration ◽  
Who Grade ◽  
Genome Atlas

Abstract Background Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion TOX has the potential to be a new prognostic marker for GBM.

The gene coding for secreted phosphoprotein1/osteopontin is the most overexpressed gene in cholangiocarcinoma—detected by oligonucleotide arrays and LightCycler analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10036-10036
Author(s):  
H. G. Hass ◽  
J. Jobst ◽  
O. Nehls ◽  
A. Frilling ◽  
J. T. Hartmann ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Cell Phenotype ◽  
Oligonucleotide Arrays ◽  
Surface Receptors ◽  
Malignant Liver ◽  
And Control

10036 Background: Cholangiocarcinomas (CCC) are the second most common primary hepatic malignancy with a still poor prognosis and arise from biliary epithelia or cholangiocytes. Until now, less is known about the molecular pathways leeding to CCC. Methods: Oligonucleotide arrays were used to analyze gene expression profiles of 8 intrahepatic CCCs. After isolation of tRNA and transcription into cDNA, biotin-labelled cRNA probes were hybridized to GeneArrays (Affymetrix U 133A) containing probes of more than 22.000 genes/ESTs. For two-dimensional cluster analysis we used special software programs (Genexplore, GeneSpring). Dysregulated genes were determined by presence in more than 70% and a 2-fold change in relation to the corresponding non-malignant liver tissue. Lightcycler analysis were performed to validate the expression datas of dysregulated genes. Results: A total of 694 dysregulated genes (330 up-/364 down-regulated, compared with corresponding non-malignant tissue) were detected. As the gene with the highest and most consistent upregulation we were able to identify osteopontin (OPN) with an average 5-fold overexpression in all CCC tissues. OPN is an acidic phosphoprotein that is secreted by osteoblasts, macrophages and many other cell types and binds to a variety of cell surface receptors (integrins/CD44). OPN is multifunctional, with activities in cell migration, regulation of bone metabolism, immune cell function and control of tumor cell phenotype. Elevated OPN levels were seen in different tumors but until now no data exist about the expression in CCCs. As one possible interaction in human carcinogenesis, OPN has recently been shown to be a novel substrate for some MMPs, which play an importand role in tumor invasion and metastasis. Conclusions: This is the first report about an overexpression of OPN in CCC and our data indicate an important role in cholangiocarcinogenesis. Further studies are needed to illucidate the moleculargenetic mechanisms of OPN interactions in CCC. No significant financial relationships to disclose.

Emerging Mechanisms of Immunosuppression in Oral Cancers

2006 ◽  
Vol 85 (12) ◽  
pp. 1061-1073 ◽  
Author(s):  
A. Jewett ◽  
C. Head ◽  
N.A. Cacalano
Keyword(s):  
Oral Cancer ◽  
Immune Responses ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Oral Cancers ◽  
Oral Cancer Patients ◽  
And Function

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients. Several mechanisms have been proposed for the functional deficiencies of tumor-associated immune cells in oral cancer patients. Both soluble factors and contact-mediated immunosuppression by the tumor cells have been implicated in the inhibition of immune cell function and the progression of tumors. More recently, elevated levels and function of key transcription factors in tumor cells, particularly NFκB and STAT3, have been shown to mediate immune suppression in the tumor microenvironment. This review will focus on these emerging mechanisms of immunosuppression in oral cancers.

scholarly journals Fibroblasts – the neglected cell type in peripheral sensitization and chronic pain? - A systematic view on the current state of the literature

2021 ◽  
Author(s):  
Naomi Shinotsuka ◽  
Franziska Denk
Keyword(s):  
Chronic Pain ◽  
Cell Function ◽  
Immune Cell ◽  
Data Extraction ◽  
Cell Types ◽  
Extraction Methods ◽  
Peripheral Sensitization ◽  
Cell Type ◽  
Systematic Screening ◽  
Pain Research

AbstractChronic pain and its underlying biological mechanisms have been studied for many decades, with a myriad of molecules, receptors and cell types known to contribute to abnormal pain sensations. We now know that besides an obvious role for neuronal populations in the peripheral and central nervous system, immune cells like microglia, macrophages and T cells are also important drivers of persistent pain. While neuroinflammation has therefore been widely studied in pain research, there is one cell-type that appears to be rather neglected in this context: the humble fibroblast.Fibroblasts may seem unassuming, but actually play a major part in regulating immune cell function and driving chronic inflammation. What is known about them in the context chronic pain?Here we set out to analyze the literature on this topic – using systematic screening and data extraction methods to obtain a balanced view on what has been published. We found that there has been surprisingly little research in this area: 134 articles met our inclusion criteria, only a tiny minority of which directly investigated interactions between fibroblasts and peripheral neurons. We categorized the articles we included – stratifying them according to what was investigated, the estimated quality of results, and any common conclusions.Fibroblasts are a ubiquitous cell type and a prominent source of many pro-algesic mediators in a wide variety of tissues. We think that they deserve a more central role in pain research and propose a new, testable model of how fibroblasts might drive peripheral neuron sensitization.

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