scholarly journals The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hendrik J. P. van der Zande ◽  
Dominik Nitsche ◽  
Laura Schlautmann ◽  
Bruno Guigas ◽  
Sven Burgdorf
Keyword(s):  
Immune Cells ◽  
Antigen Processing ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Mannose Receptor ◽  
Soluble Form ◽  
Activated T Cells ◽  
Antigen Presenting ◽  
Antigen Processing And Presentation

The mannose receptor is a member of the C-type lectin (CLEC) family, which can bind and internalize a variety of endogenous and pathogen-associated ligands. Because of these properties, its role in endocytosis as well as antigen processing and presentation has been studied intensively. Recently, it became clear that the mannose receptor can directly influence the activation of various immune cells. Cell-bound mannose receptor expressed by antigen-presenting cells was indeed shown to drive activated T cells towards a tolerogenic phenotype. On the other hand, serum concentrations of a soluble form of the mannose receptor have been reported to be increased in patients suffering from a variety of inflammatory diseases and to correlate with severity of disease. Interestingly, we recently demonstrated that the soluble mannose receptor directly promotes macrophage proinflammatory activation and trigger metaflammation. In this review, we highlight the role of the mannose receptor and other CLECs in regulating the activation of immune cells and in shaping inflammatory responses.

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 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 GITR-GITRL System, A Novel Player in Shock and Inflammation

2007 ◽  
Vol 7 ◽  
pp. 533-566 ◽  
Author(s):  
Ludovic Tibor Krausz ◽  
Rodolfo Bianchini ◽  
Simona Ronchetti ◽  
Katia Fettucciari ◽  
Giuseppe Nocentini ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Tumor Necrosis Factor Receptor ◽  
Early Response ◽  
System A ◽  
Antigen Presenting

Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor necrosis factor receptor superfamily that modulates acquired and natural immune response. It is expressed in several cells and tissues, including T cells, natural killer cells, and, at lower levels, in cells of innate immunity. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting and endothelial cells. Recent evidence suggests that the GITR/GITRL system participates in the development of inflammatory responses, including shock, either due to early response of neutrophils and macrophages, or together with autoimmune/allergic pathogenesis. The pro-inflammatory role of the GITR/GITRL system is due to: 1) modulation of the extravasation process, 2) activation of innate immunity cells, 3) activation of effector T cells also favored by partial inhibition of suppressor T cells and modulation of dendritic function. This review summarizes thein vivorole of the GITR/GITRL system in inflammation and shock, explaining the mechanisms responsible for their effects, considering the interplay among the different cells of the immune system and transduction pathways activated by GITR and GITRL triggering. The hidden aspects about GITR/GITRL function, crucial for treatment planning of inflammatory diseases and shock by modulation of this system is stressed.

scholarly journals New insights suggesting a possible role of a heat shock protein 70-kD family-related protein in antigen processing/presentation phenomenon in humans

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2865-2871 ◽  
Author(s):  
GC Manara ◽  
P Sansoni ◽  
L Badiali-De Giorgi ◽  
G Gallinella ◽  
C Ferrari ◽  
...  
Keyword(s):  
Cell Surface ◽  
Antigen Processing ◽  
Potential Role ◽  
Related Protein ◽  
Functional Studies ◽  
Recall Antigen ◽  
Normal Human ◽  
Antigen Presenting ◽  
Antigen Processing And Presentation

Abstract A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface- localized PBP72/74-related protein could play a role in antigen presentation.

Role of MIF in myocardial ischaemia and infarction: insight from recent clinical and experimental findings

2014 ◽  
Vol 127 (3) ◽  
pp. 149-161 ◽  
Author(s):  
Nalin H. Dayawansa ◽  
Xiao-Ming Gao ◽  
David A. White ◽  
Anthony M. Dart ◽  
Xiao-Jun Du
Keyword(s):  
Myocardial Ischaemia ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Metabolic Activation ◽  
Infarct Healing ◽  
Acute Mi ◽  
Antioxidative Stress ◽  
Experimental Findings

First discovered in 1966 as an inflammatory cytokine, MIF (macrophage migration inhibitory factor) has been extensively studied for its pivotal role in a variety of inflammatory diseases, including rheumatoid arthritis and atherosclerosis. Although initial studies over a decade ago reported increases in circulating MIF levels following acute MI (myocardial infarction), the dynamic changes in MIF and its pathophysiological significance following MI have been unknown until recently. In the present review, we summarize recent experimental and clinical studies examining the diverse functions of MIF across the spectrum of acute MI from brief ischaemia to post-infarct healing. Following an acute ischaemic insult, MIF is rapidly released from jeopardized cardiomyocytes, followed by a persistent MIF production and release from activated immune cells, resulting in a sustained increase in circulating levels of MIF. Recent studies have documented two distinct actions of MIF following acute MI. In the supra-acute phase of ischaemia, MIF mediates cardioprotection via several distinct mechanisms, including metabolic activation, apoptosis suppression and antioxidative stress. In prolonged myocardial ischaemia, however, MIF promotes inflammatory responses with largely detrimental effects on cardiac function and remodelling. The pro-inflammatory properties of MIF are complex and involve MIF derived from cardiac and immune cells contributing sequentially to the innate immune response evoked by MI. Emerging evidence on the role of MIF in myocardial ischaemia and infarction highlights a significant potential for the clinical use of MIF agonists or antagonists and as a unique cardiac biomarker.

scholarly journals New insights suggesting a possible role of a heat shock protein 70-kD family-related protein in antigen processing/presentation phenomenon in humans

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2865-2871
Author(s):  
GC Manara ◽  
P Sansoni ◽  
L Badiali-De Giorgi ◽  
G Gallinella ◽  
C Ferrari ◽  
...  
Keyword(s):  
Cell Surface ◽  
Antigen Processing ◽  
Potential Role ◽  
Related Protein ◽  
Functional Studies ◽  
Recall Antigen ◽  
Normal Human ◽  
Antigen Presenting ◽  
Antigen Processing And Presentation

A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface- localized PBP72/74-related protein could play a role in antigen presentation.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

scholarly journals Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1674
Author(s):  
Sara Tomei ◽  
Ola Ibnaof ◽  
Shilpa Ravindran ◽  
Soldano Ferrone ◽  
Cristina Maccalli
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Aberrant Expression ◽  
Immunological Profile ◽  
Malignant Lesions ◽  
Novel Therapeutic Strategies ◽  
Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

scholarly journals The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Se Eun Byeon ◽  
Young-Su Yi ◽  
Jueun Oh ◽  
Byong Chul Yoo ◽  
Sungyoul Hong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Src Kinase ◽  
Multiple Roles ◽  
Cellular Migration ◽  
Pharmaceutical Drugs ◽  
Tyrosine Protein Kinase

Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.

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