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Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021
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Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 20735

Special Issue Editor

Prof. Dr. Toshio Hattori

E-Mail Website
Guest Editor
Department of Health Science and Social Welfare, Kibi International University, Takahashi 716-8508, Japan
Interests: infectious diseases; tuberculosis; retrovirus; dengue; osteopontin; galectin-9
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glycans are essential to proper animal development and cellular differentiation, but they are also involved in many pathogenic processes, including inflammation, tumor, microbial, and parasitic pathogenesis. Glycan-binding proteins (GBPs or lectins) are expressed by all types of cells and a growing class of bio-active proteins. The focus of this Special Issue is galectin, a lectin family that is defined by the presence of a highly conserved ~130 amino acid carbohydrate recognition domain (CRD) that recognizes β-galactoside residues . Evolutionarily, galectins are also conserved in many phyla, including birds, amphibians, fish, nematodea, drosophila, sponges, and fungi. There are 15 different subtypes in this family that have been identified in a wide variety of human cells and tissues. Galectins are stored in the cytoplasm of many types of immune and stromal cells that occur at the entry sites of pathogenic micro-organisms, including fibroblasts, keratinocytes, endothelial cells, and mucosal membrane epithelial cells. Despite the highly conserved nature of galectin CRDs, subtle yet significant differences occur in the binding affinity between different members of the galectin protein family. Galectins are present inside the cytosol, close to the cellular membrane, or in the extracellular space, showing that they are probably released via non-classical secretory pathways and are involved in the control of RNA splicing, intracellular regulation of apoptotic signaling, and endocytic machinery and trafficking.  Galectins are also released from injured cells and express a variety of activities under pathological conditions. This Special Issue aims to present studies that describe novel aspects of galectins.

Prof. Toshio Hattori
Guest Editor

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Keywords

  • infectious disease
  • cancer
  • inflammation
  • apoptosis

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Published Papers (6 papers)

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Editorial

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3 pages, 197 KiB  
Editorial
Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021
by Toshio Hattori
Biomolecules 2022, 12(9), 1255; https://doi.org/10.3390/biom12091255 - 7 Sep 2022
Cited by 1 | Viewed by 1319
Abstract
Galectins constitute a protein family of soluble and non-glycosylated animal lectins that show a β-galactoside-binding activity via a conserved sequence of approximately 130–140 amino acids located in the carbohydrate recognition domain (CRD) [...] Full article
(This article belongs to the Special Issue Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021)

Research

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15 pages, 1594 KiB  
Article
Diagnostic Significance of Serum Galectin-3 in Hospitalized Patients with COVID-19—A Preliminary Study
by Beata Kuśnierz-Cabala, Barbara Maziarz, Paulina Dumnicka, Marcin Dembiński, Maria Kapusta, Monika Bociąga-Jasik, Marek Winiarski, Aleksander Garlicki, Tomasz Grodzicki and Michał Kukla
Biomolecules 2021, 11(8), 1136; https://doi.org/10.3390/biom11081136 - 1 Aug 2021
Cited by 23 | Viewed by 3825
Abstract
Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation leading to organ injury, including respiratory failure. Galectin-3 was implicated in innate immunological response to infections and in chronic fibrosis. The aim of our preliminary study was the assessment of the diagnostic utility of [...] Read more.
Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation leading to organ injury, including respiratory failure. Galectin-3 was implicated in innate immunological response to infections and in chronic fibrosis. The aim of our preliminary study was the assessment of the diagnostic utility of serum galectin-3 in patients with COVID-19. The prospective observational study included adult patients admitted with active COVID-19 and treated in tertiary hospital between June and July 2020. The diagnosis was confirmed by the quantitative detection of nucleic acid of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal swabs. Galectin-3 was measured by enzyme immunoassay in serum samples obtained during the first five days of hospital stay. We included 70 patients aged 25 to 73 years; 90% had at least one comorbidity. During the hospital stay, 32.9% were diagnosed with COVID-19 pneumonia and 12.9% required treatment in the intensive care unit (ICU). Serum galectin-3 was significantly increased in patients who developed pneumonia, particularly those who required ICU admission. Positive correlations were found between galectin-3 and inflammatory markers (interleukin-6, C-reactive protein, ferritin, pentraxin-3), a marker of endothelial injury (soluble fms-like tyrosine kinase-1), and a range of tissue injury markers. Serum galectin-3 enabled the diagnosis of pneumonia with moderate diagnostic accuracy and the need for ICU treatment with high diagnostic accuracy. Our findings strengthen the hypothesis that galectin-3 may be involved in severe COVID-19. Further studies are planned to confirm the preliminary results and to verify possible associations of galectin-3 with long-term consequences of COVID-19, including pulmonary fibrosis. Full article
(This article belongs to the Special Issue Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021)
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16 pages, 4239 KiB  
Article
Analysis of the Correlation of Galectin-3 Concentration with the Measurements of Echocardiographic Parameters Assessing Left Atrial Remodeling and Function in Patients with Persistent Atrial Fibrillation
by Paweł Wałek, Urszula Grabowska, Elżbieta Cieśla, Janusz Sielski, Joanna Roskal-Wałek and Beata Wożakowska-Kapłon
Biomolecules 2021, 11(8), 1108; https://doi.org/10.3390/biom11081108 - 28 Jul 2021
Cited by 10 | Viewed by 2521
Abstract
Galectin-3 (gal-3) is a fibrosis marker and may play a role in fibrosis of the left atrium (LA). Left atrial wall fibrosis may influence the transition from paroxysmal to non-paroxysmal atrial fibrillation (AF). In this study, we assessed the correlation of gal-3 concentration [...] Read more.
Galectin-3 (gal-3) is a fibrosis marker and may play a role in fibrosis of the left atrium (LA). Left atrial wall fibrosis may influence the transition from paroxysmal to non-paroxysmal atrial fibrillation (AF). In this study, we assessed the correlation of gal-3 concentration with the main echocardio-graphic parameters evaluating dimensions, volume, compliance, and left atrial contractility during AF and after successful electrical cardioversion (DCCV). The study included 63 patients with left atrial enlargement who qualified for DCCV due to persistent AF. The procedure recovered sinus rhythm in 43 (68.3%) patients. The concentration of gal-3 was negatively correlated with the echocardiographic parameters of LA including dimensions (LA length pre, rho = −0.38; p = 0.003), volume (LAV pre, rho = −0.39; p = 0.003), compliance (LASr mean post, rho = −0.33) and contractility (pLASRct mean post, rho = −0.33; p = 0.038). Negative correlations of gal-3 concentration were also observed in relation to the volume and contractility of the left ventricle. The concentration of gal-3 significantly negatively correlates with the size, systolic function, and compliance of the LA wall in patients with persistent AF. Determining gal-3 concentration in patients with persistent AF may help in the assessment of remodeling of the LA wall. Full article
(This article belongs to the Special Issue Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021)
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18 pages, 2428 KiB  
Article
Influence of Galectin-9 Treatment on the Phenotype and Function of NK-92MI Cells in the Presence of Different Serum Supplements
by Matyas Meggyes, David U Nagy, Timea Balassa, Krisztina Godony, Agnes Peterfalvi, Laszlo Szereday and Beata Polgar
Biomolecules 2021, 11(8), 1066; https://doi.org/10.3390/biom11081066 - 22 Jul 2021
Cited by 4 | Viewed by 3518
Abstract
Galectins are one of the critical players in the tumor microenvironment–tumor crosstalk and the regulation of local immunity. Galectin-9 has been in the limelight in tumor immunology. Galectin-9 possesses its multiplex biological functions both extracellularly and intracellularly, plays a pivotal role in the [...] Read more.
Galectins are one of the critical players in the tumor microenvironment–tumor crosstalk and the regulation of local immunity. Galectin-9 has been in the limelight in tumor immunology. Galectin-9 possesses its multiplex biological functions both extracellularly and intracellularly, plays a pivotal role in the modulation of adaptive and innate immunity, and induces immune tolerance. NK-92MI cell lines against different malignancies were extensively studied, and recently published trials used genetically chimeric antigen receptor-transfected NK-92MI cells in tumor immunotherapy. Besides the intensive research in tumor immunotherapy, limited information is available on their immune-checkpoint expression and the impact of checkpoint ligands on their effector functions. To uncover the therapeutic potential of modulating Galectin-9-related immunological pathways in NK-cell-based therapy, we investigated the dose-dependent effect of soluble Galectin-9 on the TIM-3 checkpoint receptor and NKG2D, CD69, FasL, and perforin expression of NK-92MI cells. We also examined how their cytotoxicity and cytokine production was altered after Gal-9 treatment and in the presence of different serum supplements using flow cytometric analysis. Our study provides evidence that the Galectin-9/TIM-3 pathway plays an important role in the regulation of NK cell function, and about the modulatory role of Galectin-9 on the cytotoxicity and cytokine production of NK-92MI cells in the presence of different serum supplements. We hope that our results will aid the development of novel NK-cell-based strategies that target Galectin-9/TIM-3 checkpoint in tumors resistant to T-cell-based immunotherapy. Full article
(This article belongs to the Special Issue Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021)
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13 pages, 2093 KiB  
Article
Exploration of Galectin Ligands Displayed on Gram-Negative Respiratory Bacterial Pathogens with Different Cell Surface Architectures
by María A. Campanero-Rhodes, Ioanna Kalograiaki, Begoña Euba, Enrique Llobet, Ana Ardá, Jesús Jiménez-Barbero, Junkal Garmendia and Dolores Solís
Biomolecules 2021, 11(4), 595; https://doi.org/10.3390/biom11040595 - 18 Apr 2021
Cited by 6 | Viewed by 3257
Abstract
Galectins bind various pathogens through recognition of distinct carbohydrate structures. In this work, we examined the binding of four human galectins to the Gram-negative bacteria Klebsiella pneumoniae (Kpn) and non-typeable Haemophilus influenzae (NTHi), which display different surface glycans. In particular, Kpn cells are [...] Read more.
Galectins bind various pathogens through recognition of distinct carbohydrate structures. In this work, we examined the binding of four human galectins to the Gram-negative bacteria Klebsiella pneumoniae (Kpn) and non-typeable Haemophilus influenzae (NTHi), which display different surface glycans. In particular, Kpn cells are covered by a polysaccharide capsule and display an O-chain-containing lipopolysaccharide (LPS), whereas NTHi is not capsulated and its LPS, termed lipooligosacccharide (LOS), does not contain O-chain. Binding assays to microarray-printed bacteria revealed that galectins-3, -4, and -8, but not galectin-1, bind to Kpn and NTHi cells, and confocal microscopy attested binding to bacterial cells in suspension. The three galectins bound to array-printed Kpn LPS. Moreover, analysis of galectin binding to mutant Kpn cells evidenced that the O-chain is the docking point for galectins on wild type Kpn. Galectins-3, -4, and -8 also bound the NTHi LOS. Microarray-assisted comparison of the binding to full-length and truncated LOSs, as well as to wild type and mutant cells, supported LOS involvement in galectin binding to NTHi. However, deletion of the entire LOS oligosaccharide chain actually increased binding to NTHi cells, indicating the availability of other ligands on the bacterial surface, as similarly inferred for Kpn cells devoid of both O-chain and capsule. Altogether, the results illustrate galectins’ versatility for recognizing different bacterial structures, and point out the occurrence of so far overlooked galectin ligands on bacterial surfaces. Full article
(This article belongs to the Special Issue Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021)
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Review

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13 pages, 1471 KiB  
Review
Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment
by Yanyu Huang, Hsiao-Chi Wang, Junwei Zhao, Ming-Heng Wu and Tsung-Chieh Shih
Biomolecules 2021, 11(10), 1398; https://doi.org/10.3390/biom11101398 - 23 Sep 2021
Cited by 30 | Viewed by 4880
Abstract
Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. [...] Read more.
Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. Tumor-secreted Gal-1 can bind to glycosylated receptors on immune cells and trigger the suppression of immune cell function in the tumor microenvironment, contributing to the immune evasion of tumors. The aim of this review is to summarize the current literature on the expression and function of Gal-1 in the human tumor microenvironment, as well as therapeutics targeting Gal-1. Full article
(This article belongs to the Special Issue Galectins: Their Network and Roles in Infection/Immunity/Tumor Growth Control 2021)
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