scholarly journals The Trypanosoma brucei-Derived Ketoacids, Indole Pyruvate and Hydroxyphenylpyruvate, Induce HO-1 Expression and Suppress Inflammatory Responses in Human Dendritic Cells

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 164
Author(s):  
Hannah K. Fitzgerald ◽  
Sinead A. O’Rourke ◽  
Eva Desmond ◽  
Nuno G. B. Neto ◽  
Michael G. Monaghan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Trypanosoma Brucei ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Heme Oxygenase 1 ◽  
Inflammatory Conditions ◽  
High Concentrations ◽  
Inflammatory Profile ◽  
Human Dendritic Cells

The extracellular parasite and causative agent of African sleeping sickness Trypanosoma brucei (T. brucei) has evolved a number of strategies to avoid immune detection in the host. One recently described mechanism involves the conversion of host-derived amino acids to aromatic ketoacids, which are detected at relatively high concentrations in the bloodstream of infected individuals. These ketoacids have been shown to directly suppress inflammatory responses in murine immune cells, as well as acting as potent inducers of the stress response enzyme, heme oxygenase 1 (HO-1), which has proven anti-inflammatory properties. The aim of this study was to investigate the immunomodulatory properties of the T. brucei-derived ketoacids in primary human immune cells and further examine their potential as a therapy for inflammatory diseases. We report that the T. brucei-derived ketoacids, indole pyruvate (IP) and hydroxyphenylpyruvate (HPP), induce HO-1 expression through Nrf2 activation in human dendritic cells (DC). They also limit DC maturation and suppress the production of pro-inflammatory cytokines, which, in turn, leads to a reduced capacity to differentiate adaptive CD4+ T cells. Furthermore, the ketoacids are capable of modulating DC cellular metabolism and suppressing the inflammatory profile of cells isolated from patients with inflammatory bowel disease. This study therefore not only provides further evidence of the immune-evasion mechanisms employed by T. brucei, but also supports further exploration of this new class of HO-1 inducers as potential therapeutics for the treatment of inflammatory conditions.

scholarly journals Regulatory NLRs Control the RLR-Mediated Type I Interferon and Inflammatory Responses in Human Dendritic Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Tünde Fekete ◽  
Dora Bencze ◽  
Attila Szabo ◽  
Eszter Csoma ◽  
Tamas Biro ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Type I ◽  
Human Dendritic Cells

scholarly journals Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated with the Airway Microbiota

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31976 ◽  
Author(s):  
Jeppe Madura Larsen ◽  
Daniel Bisgaard Steen-Jensen ◽  
Janne Marie Laursen ◽  
Jonas Nørskov Søndergaard ◽  
Hanieh Sadat Musavian ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Pathogenic Bacteria ◽  
Inflammatory Profile ◽  
Human Dendritic Cells

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

scholarly journals Co-operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis

Immunology ◽  
2016 ◽  
Vol 150 (3) ◽  
pp. 312-328 ◽  
Author(s):  
Andrew R. Williams ◽  
Elsenoor J. Klaver ◽  
Lisa C. Laan ◽  
Aina Ramsay ◽  
Christos Fryganas ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Parasitic Nematode ◽  
Inflammatory Responses ◽  
Trichuris Suis ◽  
Human Dendritic Cells

scholarly journals HDL in Immune-Inflammatory Responses: Implications beyond Cardiovascular Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1061
Author(s):  
Fabrizia Bonacina ◽  
Angela Pirillo ◽  
Alberico L. Catapano ◽  
Giuseppe D. Norata
Keyword(s):  
Immune Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Membrane Lipid ◽  
High Density Lipoproteins ◽  
Protective Effects ◽  
The Road ◽  
Plasma Membrane Lipid ◽  
Inflammatory Burden

High density lipoproteins (HDL) are heterogeneous particles composed by a vast array of proteins and lipids, mostly recognized for their cardiovascular (CV) protective effects. However, evidences from basic to clinical research have contributed to depict a role of HDL in the modulation of immune-inflammatory response thus paving the road to investigate their involvement in other diseases beyond those related to the CV system. HDL-C levels and HDL composition are indeed altered in patients with autoimmune diseases and usually associated to disease severity. At molecular levels, HDL have been shown to modulate the anti-inflammatory potential of endothelial cells and, by controlling the amount of cellular cholesterol, to interfere with the signaling through plasma membrane lipid rafts in immune cells. These findings, coupled to observations acquired from subjects carrying mutations in genes related to HDL system, have helped to elucidate the contribution of HDL beyond cholesterol efflux thus posing HDL-based therapies as a compelling interventional approach to limit the inflammatory burden of immune-inflammatory diseases.

scholarly journals Dendritic Cells and CCR7 Expression; an Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8340
Author(s):  
Emma Probst Brandum ◽  
Astrid Sissel Jørgensen ◽  
Mette Marie Rosenkilde ◽  
Gertrud Malene Hjortø
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Antagonistic Effect ◽  
Lymphoid Tissues ◽  
Chronic Inflammatory Diseases ◽  
Inflammatory Conditions ◽  
Inflammatory State ◽  
And Control

Chemotactic cytokines—chemokines—control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body’s defense system. Many chemokines also participate in pathological processes leading up to and exacerbating the inflammatory state characterizing chronic inflammatory diseases. In this review, we discuss the role of dendritic cells (DCs) and the central chemokine receptor CCR7 in the initiation and sustainment of selected chronic inflammatory diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. We revisit the binary role that CCR7 plays in combatting and progressing cancer, and we discuss how CCR7 and DCs can be harnessed for the treatment of cancer. To provide the necessary background, we review the differential roles of the natural ligands of CCR7, CCL19, and CCL21 and how they direct the mobilization of activated DCs to lymphoid organs and control the formation of associated lymphoid tissues (ALTs). We provide an overview of DC subsets and, briefly, elaborate on the different T-cell effector types generated upon DC–T cell priming. In the conclusion, we promote CCR7 as a possible target of future drugs with an antagonistic effect to reduce inflammation in chronic inflammatory diseases and an agonistic effect for boosting the reactivation of the immune system against cancer in cell-based and/or immune checkpoint inhibitor (ICI)-based anti-cancer therapy.

scholarly journals The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Jéssica Aparecida da Silva Pereira ◽  
Felipe Corrêa da Silva ◽  
Pedro Manoel Mendes de Moraes-Vieira
Keyword(s):  
Immune Cells ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Low Grade ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Increased Risk ◽  
Inflammatory Profile ◽  
The Impact

Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorders, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GHS-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune systems to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D).

Osteopontin and Mucosal Protection

2006 ◽  
Vol 85 (5) ◽  
pp. 404-415 ◽  
Author(s):  
J. Sodek ◽  
A. Paes Batista Da Silva ◽  
R. Zohar
Keyword(s):  
Immune Cells ◽  
Barrier Function ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Proteolytic Processing ◽  
Mucosal Inflammation ◽  
Tissue Destruction ◽  
Mucosal Tissues

Protection of mucosal tissues of the oral cavity, intestines, respiratory tract, and urogenital tract from the constant challenge of pathogens is achieved by the combined barrier function of the lining epithelia and specialized immune cells. Recent studies have indicated that osteopontin (OPN) has a pivotal role in the development of immune responses and in the tissue destruction and the subsequent repair processes associated with inflammatory diseases. While expression of OPN is increased in immune cells—including neutrophils, macrophages, T- and B-lymphocytes—and in epithelial, endothelial, and fibroblastic cells of inflamed tissues, deciphering the specific functions of OPN has been difficult. In part, this is due to the broad range of biological activities of OPN that are mediated by multiple receptors which recognize several signaling motifs whose activities are influenced by post-translational modifications and proteolytic processing of OPN. Understanding the role of OPN in mucosal inflammation is further complicated by its contributions to the barrier function of the lining epithelia and the complexity of the specialized mucosal immune system. In an attempt to provide some insights into the involvement of OPN in mucosal diseases, this review summarizes current knowledge of the biological activities of OPN involved in the development of inflammatory responses and in wound healing, and indicates how these activities may affect the protection of mucosal tissues.

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