scholarly journals Activating Natural Killer Cell Receptors, Selectins, and Inhibitory Siglecs Recognize Ebolavirus Glycoprotein

2021 ◽  
pp. 1-13
Author(s):  
Mostafa Jarahian ◽  
Katharina Marstaller ◽  
Nadine Banna ◽  
Roshanak Ahani ◽  
Mohammad Hossein Etemadzadeh ◽  
...  
Keyword(s):  
Immune System ◽  
Natural Killer ◽  
Nk Cell ◽  
Lentiviral Vector ◽  
Killer Cell ◽  
Inhibitory Receptors ◽  
Binding Studies ◽  
Immune Effector ◽  
Cell Receptors ◽  
Surface Molecules

Expression of the extensively glycosylated Ebolavirus glycoprotein (EBOV-GP) induces physical alterations of surface molecules and plays a crucial role in viral pathogenicity. Here we investigate the interactions of EBOV-GP with host surface molecules using purified EBOV-GP, EBOV-GP-transfected cell lines, and EBOV-GP-pseudotyped lentiviral particles. Subsequently, we wanted to examine which receptors are involved in this recognition by binding studies to cells transfected with the EBOV-GP as well as to recombinant soluble EBOV-GP. As the viral components can also bind to inhibitory receptors of immune cells (e.g., Siglecs, TIM-1), they can even suppress the activity of immune effector cells. Our data show that natural killer (NK) cell receptors NKp44 and NKp46, selectins (CD62E/P/L), the host factors DC-SIGNR/DC-SIGN, and inhibitory Siglecs function as receptors for EBOV-GP. Our results show also moderate to strong avidity of homing receptors (P-, L-, and E-selectin) and DC-SIGNR/DC-SIGN to purified EBOV-GP, to cells transfected with EBOV-GP, as well as to the envelope of a pseudotyped lentiviral vector carrying the EBOV-GP. The concomitant activation and inhibition of the immune system exemplifies the evolutionary antagonism between the immune system and pathogens. Altogether these interactions with activating and inhibitory receptors result in a reduced NK cell-mediated lysis of EBOV-GP-expressing cells. Modulation of these interactions may provide new strategies for treating infections caused by this virus.

scholarly journals Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Endocrines ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 121-132
Author(s):  
Erik D. Hanson ◽  
Lauren C. Bates ◽  
Kaileigh Moertl ◽  
Elizabeth S. Evans
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Cancer Survivors ◽  
Nk Cells ◽  
Natural Killer ◽  
Acute Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Current Evidence ◽  
Cell Mobilization

Natural killer (NK) cells from the innate immune system are integral to overall immunity and also in managing the tumor burden during cancer. Breast (BCa) and prostate cancer (PCa) are the most common tumors in U.S. adults. Both BCa and PCa are frequently treated with hormone suppression therapies that are associated with numerous adverse effects including direct effects on the immune system. Regular exercise is recommended for cancer survivors to reduce side effects and improve quality of life. Acute exercise is a potent stimulus for NK cells in healthy individuals with current evidence indicating that NK mobilization in individuals with BCa and PCa is comparable. NK cell mobilization results from elevations in shear stress and catecholamine levels. Despite a normal NK cell response to exercise, increases in epinephrine are attenuated in BCa and PCa. The significance of this potential discrepancy still needs to be determined. However, alterations in adrenal hormone signaling are hypothesized to be due to chronic stress during cancer treatment. Additional compensatory factors induced by exercise are reviewed along with recommendations on standardized approaches to be used in exercise immunology studies involving oncology populations.

Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 1935-1947 ◽  
Author(s):  
Sherif S. Farag ◽  
Todd A. Fehniger ◽  
Loredana Ruggeri ◽  
Andrea Velardi ◽  
Michael A. Caligiuri
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Natural Cytotoxicity ◽  
Receptor Ligand ◽  
Cell Receptors ◽  
Nk Cell Receptors ◽  
Ligand Interactions ◽  
Nk Receptor

AbstractNatural killer (NK) cells have held great promise for the immunotherapy of cancer for more than 3 decades. However, to date only modest clinical success has been achieved manipulating the NK cell compartment in patients with malignant disease. Progress in the field of NK cell receptors has revolutionized our concept of how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Major families of cell surface receptors that inhibit and activate NK cells to lyse target cells have been characterized, including killer cell immunoglobulinlike receptors (KIRs), C-type lectins, and natural cytotoxicity receptors (NCRs). Further, identification of NK receptor ligands and their expression on normal and transformed cells completes the information needed to begin development of rational clinical approaches to manipulating receptor/ligand interactions for clinical benefit. Indeed, clinical data suggest that mismatch of NK receptors and ligands during allogeneic bone marrow transplantation may be used to prevent leukemia relapse. Here, we review how NK cell receptors control natural cytotoxicity and novel approaches to manipulating NK receptor-ligand interactions for the potential benefit of patients with cancer.

Anti-natural Killer Inhibitory Receptors in Elderly Patients with Acute Myeloid Leukaemia

2010 ◽  
Vol 06 (01) ◽  
pp. 86
Author(s):  
Norbert Vey ◽  
Daniel Olive ◽  
◽  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Single Agent ◽  
Inhibitory Receptors ◽  
Leukaemic Cells ◽  
Acute Myeloid

Treatment with anti-killer-cell immunoglobulin-like receptor (KIR) monoclonal antibody (mAb) is a new approach aimed at harnessing the antileukaemic potential of natural killer (NK) cells for the treatment of acute myeloid leukaemia (AML). NK cell antitumour activity is regulated by a balance between activating and inhibitory receptors (KIR). 1-7F9/IPH2101 is a fully human immunoglobulin G4 (IgG4) mAb that binds to inhibitory KIR and blocks binding with its ligand (human leukocyte antigen C [HLA-C] molecule) on leukaemic cells.In vitro,and in a surrogatein vivomodel in mice, treatment with 1-7F9/IPH2101 was able to induce NK cell activation and cytotoxicity against leukaemic cells. Patients with AML often display abnormal NK cell function, while evidence of an impact of NK cell status on AML outcome has been reported in allogeneic transplantation. 1-7F9/IPH2101 is currently under clinical investigation in patients with AML. This article reviews the mechanisms of NK cell antileukaemic activity and its role and defects in AML. Currently available data on the pre-clinical and clinical development of 1-7F9/IPH2101 are presented, and the rationale for its future use as a single agent or in combination is discussed.

scholarly journals Natural Killer Cell Inhibitory Receptors Block Actin Cytoskeleton-dependent Recruitment of 2B4 (CD244) to Lipid Rafts

2002 ◽  
Vol 197 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Carsten Watzl ◽  
Eric O. Long
Keyword(s):  
Actin Cytoskeleton ◽  
Natural Killer ◽  
Lipid Rafts ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
General Mechanism ◽  
Target Cells ◽  
Inhibitory Receptors ◽  
Detergent Resistant Membrane

A dynamic balance of positive and negative signals regulates target cell lysis by natural killer (NK) cells upon engagement of a variety of different activation receptors and of inhibitory receptors that recruit the tyrosine phosphatase SHP-1. However, the step at which activation signals are blocked by SHP-1 is not known. We have been using activation receptor 2B4 (CD244) to study the influence of inhibitory receptors on NK cell activation. Engagement of inhibitory receptors by HLA class I on target cells blocks phosphorylation of 2B4, placing the inhibitory step at the level, or upstream of 2B4 phosphorylation. Here we show that phosphorylated 2B4, after engagement with either antibodies or target cells that express the 2B4 ligand, is found exclusively in a detergent-resistant membrane fraction that contains lipid rafts. Integrity of lipid rafts was essential for phosphorylation and activating function of 2B4. Coengagement of inhibitory receptors blocked 2B4 phosphorylation and 2B4 association with detergent-resistant membranes, indicating that inhibitory receptors function upstream of raft-dependent signals. Recruitment of 2B4 into detergent-resistant membrane fractions and 2B4 phosphorylation were dependent on actin polymerization. Blocking actin cytoskeleton-dependent raft recruitment of different receptors may be a general mechanism by which inhibitory receptors control NK cell activation.

scholarly journals Natural Killer Cell Diversity in Viral Infection: Why and How Much?

2016 ◽  
Vol 1 (1) ◽  
pp. 165 ◽  
Author(s):  
Catherine A. Blish
Keyword(s):  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Expression Patterns ◽  
Killer Cell ◽  
Inhibitory Receptors ◽  
Cell Repertoire ◽  
Cell Diversity ◽  
Repertoire Diversity ◽  
Functional Consequences

Natural killer cells are a diverse group of innate lymphocytes that are specialized to rapidly respond to cancerous or virus-infected cells. NK cell function is controlled by the integration of signals from activating and inhibitory receptors expressed at the cell surface. Variegated expression patterns of these activating and inhibitory receptors at the single cell level leads to a highly diverse NK cell repertoire. Here I review the factors that influence NK cell repertoire diversity and its functional consequences for our ability to fight viruses.

Effect of Conventional Chemotherapies on Natural Killer Cell Activity

2021 ◽  
Vol 17 ◽  
Author(s):  
Idris Kirhan ◽  
Huseyin Taskiran ◽  
Ataman Gönel
Keyword(s):  
Immune System ◽  
Natural Killer ◽  
Cancer Patients ◽  
Nk Cell ◽  
Metastatic Cancer ◽  
Critical Role ◽  
Killer Cell ◽  
Cell Activity ◽  
Activity Levels ◽  
Nk Cell Activity

Background: The effects of chemotherapeutics agents are considered to influence immune system and cells due to their myelosuppressive and immunosuppressive functions. Natural Killer Cells are one of the important components of innate immune system and have a critical role against tumor cells and infections. Objective: The study was aimed to demonstrate whether conventional chemotherapies had an effect on Natural Killer (NK) cell activity. Methods: 49 adjuvant, 19 first time metastatic chemotherapy-naïve cancer patients were recruited into the study. Pre-chemotherapy and post-chemotherapy, at 1th and 4th cycles, blood samples were obtained for NK cell activity. Results: We found no difference between baseline and post-chemotherapy NK cell activity levels. In addition, we found no difference between pre-chemotherapy and post-chemotherapy NK cell activity in both adjuvant and metastatic cancer patients separately. Conclusion: Conventional chemotherapy seems to no affect NK cell activity levels in cancer patients in both metastatic and adjuvant settings.

scholarly journals Inhibitory Receptors Alter Natural Killer Cell Interactions with Target Cells Yet Allow Simultaneous Killing of Susceptible Targets

1999 ◽  
Vol 190 (7) ◽  
pp. 1005-1012 ◽  
Author(s):  
Mikael Eriksson ◽  
Guenther Leitz ◽  
Erik Fällman ◽  
Ove Axner ◽  
James C. Ryan ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mhc Class I ◽  
Optical Tweezers ◽  
Target Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Class I ◽  
Target Cells ◽  
Inhibitory Receptors

Inhibitory receptors expressed on natural killer (NK) cells abrogate positive signals upon binding corresponding major histocompatibility complex (MHC) class I molecules on various target cells. By directly micromanipulating the effector–target cell encounter using an optical tweezers system which allowed temporal and spatial control, we demonstrate that Ly49–MHC class I interactions prevent characteristic cellular responses in NK cells upon binding to target cells. Furthermore, using this system, we directly demonstrate that an NK cell already bound to a resistant target cell may simultaneously bind and kill a susceptible target cell. Thus, although Ly49-mediated inhibitory signals can prevent many types of effector responses, they do not globally inhibit cellular function, but rather the inhibitory signal is spatially restricted towards resistant targets.

scholarly journals Carbohydrate intake during endurance exercise increases natural killer cell responsiveness to IL-2

2004 ◽  
Vol 96 (1) ◽  
pp. 271-275 ◽  
Author(s):  
Brian K. McFarlin ◽  
Michael G. Flynn ◽  
Laura K. Stewart ◽  
Kyle L. Timmerman
Keyword(s):  
Immune System ◽  
T Cell ◽  
Natural Killer ◽  
Endurance Exercise ◽  
Nk Cell ◽  
Venous Blood ◽  
Killer Cell ◽  
Cell Activity ◽  
Cytotoxic T Cell

The purpose of this study was to evaluate the effect of high-intensity endurance exercise and carbohydrate consumption on in vitro responsiveness of natural killer (NK) to IL-2 (2.5 U/ml for 24 h). Thirteen male subjects (18-26 yr old; peak O2consumption = 59.79 ± 5.13 ml·kg-1·ml-1) were recruited to complete two 1-h (75-80% peak O2consumption) cycling trials in a random counterbalanced order: carbohydrate (CHO) and placebo (Pla). Venous blood samples were collected before (Pre), immediately (Post), 2 h (2H), and 4 h (4H) after exercise. All resting samples were taken after 15 min of seated rest. NK (CD3-/56+), activated NK (CD3-/56+/69+), helper T cell (Th; CD3+/4+), and cytotoxic T cell (Tc; CD3+/8+) number were measured by using flow cytometry. NK cell activity (NKCA) was determined by using both a51Cr release assay (NKCA-51) and activated NK cell number (NKCA-69). Immune system variables were not different between CHO and Pla, with the exception of NK cell responsiveness to IL-2, where Post (116.2%) and 4H (48.4%) was significantly greater in CHO ( P < 0.05). NK, Th, and Tc were significantly higher Post (40.7, 102.7, and 82.0%, respectively) and lower at 2H (-51.9, -53.3, and -53.2%, respectively) than Pre (time effect). 4H was not different from Pre for NK, Th, and Tc. NKCA was significantly lower 2H (NKCA-51, NKCA-69) and 4H (NKCA-69) than Pre. CHO consumption during exercise did not prevent disruptions in unstimulated immune system function, but it did enhance NK responsiveness to IL-2.

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