scholarly journals Rapid dose-dependent Natural Killer (NK) cell modulation and cytokine responses following human rVSV-ZEBOV Ebolavirus vaccination

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
David Pejoski ◽  
◽  
Casimir de Rham ◽  
Paola Martinez-Murillo ◽  
Francesco Santoro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Nk Cell ◽  
Protective Efficacy ◽  
Innate Immune ◽  
Receptor Expression ◽  
Innate Immune Responses ◽  
Plasma Cytokines ◽  
Surface Receptor ◽  
Dose Dependent

Abstract The rVSV-ZEBOV Ebolavirus vaccine confers protection within days after immunization, suggesting the contribution of innate immune responses. We report modulation of rVSV-ZEBOV vaccinee blood CD56+ NK cell numbers, NKG2D or NKp30 surface receptor expression, Killer Immunoglobulin-like Receptor (KIR)+ cell percentages and NK-cell-related genes on day 1 post immunization. Inverse correlations existed between the concentration of several plasma cytokines and inhibitory KIR+ CD56dim or cytokine-responsive CD56bright NK cells. Thus, NK cells may contribute to the early protective efficacy of rVSV-ZEBOV in humans.

Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3851-3858 ◽  
Author(s):  
Mariella Della Chiesa ◽  
Chiara Romagnani ◽  
Andreas Thiel ◽  
Lorenzo Moretta ◽  
Alessandro Moretta
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
De Novo ◽  
Nk Cell ◽  
Innate Immune ◽  
Dependent Manner ◽  
B Cell Differentiation ◽  
Innate Immune Responses ◽  
Intrinsic Resistance

AbstractDuring innate immune responses, natural killer (NK) cells may interact with both plasmacytoid dendritic cells (pDCs) and monocyte-derived dendritic cells (MDDCs). We show that freshly isolated NK cells promote the release by pDCs of IFN-α, in a CpG-dependent manner, whereas they induce IL-6 production in a CpG-independent manner. In turn pDC-derived IFN-α up-regulates NK-mediated killing, whereas IL-6 could promote B-cell differentiation. We also show that exposure to exogenous IL-12 or coculture with maturing MDDCs up-regulates the NK-cell–dependent IFN-α production by pDCs. On the other hand, NK cells cocultured with pDCs acquire the ability to kill immature MDDCs, thus favoring their editing process. Finally, we show that activated NK cells are unable to lyse pDCs because these cells display an intrinsic resistance to lysis. The exposure of pDCs to IL-3 increased their susceptibility to NK-cell cytotoxicity resulting from a de novo expression of ligands for activating NK-cell receptors, such as the DNAM-1 ligand nectin-2. Thus, different cell-to-cell interactions and various cytokines appear to control a multidirectional network between NK cells, MDDCs, and pDCs that is likely to play an important role during the early phase of innate immune responses to viral infections and to tumors.

scholarly journals Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ji-Yoon Noh ◽  
Suk Ran Yoon ◽  
Tae-Don Kim ◽  
Inpyo Choi ◽  
Haiyoung Jung
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Immune Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Innate Immune Responses ◽  
Toll Like Receptors ◽  
Microbial Infection

Innate immunity represents the first barrier for host defense against microbial infection. Toll-like receptors (TLRs) are the most well-defined PRRs with respect to PAMP recognition and induction of innate immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and trigger innate immune responses by inducing inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. TLRs are expressed either on the cell surface or within endosomes of innate immune cells. NK cells are one of the innate immune cells and also express TLRs to recognize or respond to PAMPs. TLRs in NK cells induce the innate immune responses against bacterial and viral infections via inducing NK cytotoxicity and cytokine production. In this review, we will discuss the expression and cellular function of TLRs in NK cells and also introduce some therapeutic applications of TLR agonists for NK cell-mediated immunotherapy.

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

scholarly journals The cell surface receptor Slamf6 modulates innate immune responses duringCitrobacter rodentium-induced colitis

2015 ◽  
Vol 27 (9) ◽  
pp. 447-457 ◽  
Author(s):  
Boaz van Driel ◽  
Guoxing Wang ◽  
Gongxian Liao ◽  
Peter J. Halibozek ◽  
Marton Keszei ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Innate Immune ◽  
Cell Surface Receptor ◽  
Innate Immune Responses ◽  
Surface Receptor

scholarly journals Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality

2017 ◽  
Vol 176 (4) ◽  
pp. 471-480 ◽  
Author(s):  
Irina Bancos ◽  
Jon Hazeldine ◽  
Vasileios Chortis ◽  
Peter Hampson ◽  
Angela E Taylor ◽  
...  
Keyword(s):  
Nk Cells ◽  
Adrenal Insufficiency ◽  
Natural Killer ◽  
Nk Cell ◽  
Respiratory Infections ◽  
Immune Defense ◽  
Innate Immune ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Primary Adrenal Insufficiency

Objective Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection. Design and methods We undertook a cross-sectional study of 42 patients with PAI due to autoimmune adrenalitis (n = 37) or bilateral adrenalectomy (n = 5) and 58 sex- and age-matched controls. A comprehensive screen of innate immune function, consisting of measurements of neutrophil phagocytosis, reactive oxygen species production, NK cell cytotoxicity (NKCC) and NK cell surface receptor expression, was performed on all subjects. Results Neutrophil function did not differ between PAI and controls. However, NKCC was significantly reduced in PAI (12.0 ± 1.5% vs 21.1 ± 2.6%, P < 0.0001). Phenotypically, the percentage of NK cells expressing the activating receptors NKG2D and NKp46 was significantly lower in PAI, as was the surface density of NKG2D (all P < 0.0001). Intracellular granzyme B expression was significantly increased in NK cells from PAI patients (P < 0.01). Conclusions Adrenal insufficiency is associated with significantly decreased NKCC, thereby potentially compromising early recognition and elimination of virally infected cells. This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI.

scholarly journals The functional characterization of interleukin-10 receptor expression on human natural killer cells

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3577-3585 ◽  
Author(s):  
WE Carson ◽  
MJ Lindemann ◽  
R Baiocchi ◽  
M Linett ◽  
JC Tan ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Binding Studies ◽  
High Affinity ◽  
Functional Consequences ◽  
Dose Dependent

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.

scholarly journals Variation in Adenovirus Transgene Expression between BALB/c and C57BL/6 Mice Is Associated with Differences in Interleukin-12 and Gamma Interferon Production and NK Cell Activation

2001 ◽  
Vol 75 (10) ◽  
pp. 4540-4550 ◽  
Author(s):  
YuFeng Peng ◽  
Erik Falck-Pedersen ◽  
Keith B. Elkon
Keyword(s):  
Nk Cells ◽  
Transgene Expression ◽  
Cell Activation ◽  
Cell Function ◽  
Nk Cell ◽  
Gamma Interferon ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Mouse Strains ◽  
Innate Immune Responses

ABSTRACT The innate immune response against replication-defective adenoviruses (Ad) is poorly defined. We and others have previously observed striking differences in the rate at which the Ad vector itself or the virus encoding a variety of transgenes is eliminated in different mouse strains. Here, we report that Ad infection of BALB/ mice is associated with sixfold-higher levels of serum alanine aminotransferase and that Ad transgenes induce two- to threefold-higher levels of intrahepatic NK cells and NK activity compared to C57BL/6 mice. The increase in NK activation in BALB/c mice was associated with ∼4-fold higher level of mRNA expression of a newly described NKG2 receptor activator, H-60, as well as increased expression of interleukin-12 and gamma interferon mRNAs in BALB/c mice compared to C57BL/6 mice. NK depletion in BALB/c mice or defective NK function in C3H beige mice extended transgene expression compared to their appropriate controls, and attenuation of NK together with CD8 T-cell function had a synergistic effect. These findings indicate that there are intrinsic differences in the innate immune responses of different mouse strains to Ad and Ad transgenes and that NK cells, in cooperation with CD8 T cells, play a pivotal role in the early extinction of transgene expression in BALB/c mice.

scholarly journals Role for TLR2 in NK Cell-Mediated Control of Murine Cytomegalovirus In Vivo

2006 ◽  
Vol 80 (9) ◽  
pp. 4286-4291 ◽  
Author(s):  
Eva Szomolanyi-Tsuda ◽  
Xueya Liang ◽  
Raymond M. Welsh ◽  
Evelyn A. Kurt-Jones ◽  
Robert W. Finberg
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Innate Immune ◽  
Murine Cytomegalovirus ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Mcmv Infection ◽  
Toll Like Receptor 2 ◽  
Antiviral Control

ABSTRACT Natural killer (NK) cells are essential for the early control of murine cytomegalovirus (MCMV) infection. Here, we demonstrate that toll-like receptor 2 (TLR2) plays a role in the NK cell-mediated control of MCMV. TLR2 knockout (KO) mice had elevated levels of MCMV in the spleen and liver on day 4 postinfection compared to C57BL/6 mice. In vivo depletion of NK cells with anti-NK1.1 antibodies, however, eliminated the differences in viral titers between the two groups, suggesting that the effect of TLR2 on MCMV clearance on day 4 was NK cell mediated. The defect in early antiviral control was associated with a decreased NK cell population in the spleen and liver and reduced amounts of interleukin-18 and α/β interferon secreted in the TLR2 KO mice. Our studies suggest that in addition to the reported involvement of TLR9 and TLR3, TLR2 is also involved in innate immune responses to MCMV infection.

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