Natural Killer Cells: From Innate to Adaptive Features

2021 ◽  
Vol 39 (1) ◽  
pp. 417-447
Author(s):  
Adriana M. Mujal ◽  
Rebecca B. Delconte ◽  
Joseph C. Sun
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Host Defense ◽  
Nk Cell ◽  
Clonal Expansion ◽  
Cell Mediated Immunity ◽  
Adaptive Responses ◽  
Adaptive Immune ◽  
Effector Activity ◽  
Innate Lymphocytes

Natural killer (NK) cells are innate lymphocytes that provide critical host defense against pathogens and cancer. Originally heralded for their early and rapid effector activity, NK cells have been recognized over the last decade for their ability to undergo adaptive immune processes, including antigen-driven clonal expansion and generation of long-lived memory. This review presents an overview of how NK cells lithely partake in both innate and adaptive responses and how this versatility is manifest in human NK cell–mediated immunity.

scholarly journals Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation

2014 ◽  
Vol 211 (12) ◽  
pp. 2455-2465 ◽  
Author(s):  
Tsukasa Nabekura ◽  
Lewis L. Lanier
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Host Defense ◽  
Nk Cell ◽  
Microbial Pathogens ◽  
Secondary Response ◽  
Hematopoietic Stem ◽  
Adaptive Immune ◽  
Specific Expansion ◽  
Important Host

Natural killer (NK) cells provide important host defense against microbial pathogens and can generate a population of long-lived memory NK cells after infection or immunization. Here, we addressed whether NK cells can expand and differentiate after alloantigen stimulation, which may be important in hematopoietic stem cell and solid tissue transplantation. A subset of NK cell in C57BL/6 mice expresses the activating Ly49D receptor that is specific for H-2Dd. These Ly49D+ NK cells can preferentially expand and differentiate when challenged with allogeneic H-2Dd cells in the context of an inflammatory environment. H-2Dd is also recognized by the inhibitory Ly49A receptor, which, when coexpressed on Ly49D+ NK cells, suppresses the expansion of Ly49D+ NK cells. Specificity of the secondary response of alloantigen-primed NK cells was defined by the expression of activating Ly49 receptors and regulated by the inhibitory receptors for MHC class I. Thus, the summation of signals through a repertoire of Ly49 receptors controls the adaptive immune features of NK cells responding to allogeneic cells.

scholarly journals Dysregulation of Natural Killer Cells in Obesity

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 573 ◽  
Author(s):  
Donal O’Shea ◽  
Andrew E. Hogan
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Viral Infections ◽  
Nk Cell ◽  
Viral Immunity ◽  
Host Protection ◽  
Cell Functions ◽  
Innate Lymphocytes ◽  
The Impact

Natural killer (NK) cells are a population of lymphocytes which classically form part of the innate immune system. They are defined as innate lymphocytes, due to their ability to kill infected or transformed cells without prior activation. In addition to their cytotoxic abilities, NK cells are also rapid producers of inflammatory cytokines such as interferon gamma (IFN-γ) and are therefore a critical component of early immune responses. Due to these unique abilities, NK cells are a very important component of host protection, especially anti-tumour and anti-viral immunity. Obesity is a worldwide epidemic, with over 600 million adults and 124 million children now classified as obese. It is well established that individuals who are obese are at a higher risk of many acute and chronic conditions, including cancer and viral infections. Over the past 10 years, many studies have investigated the impact of obesity on NK cell biology, detailing systemic dysregulation of NK cell functions. More recently, several studies have investigated the role of NK cells in the homeostasis of adipose tissue and the pathophysiology of obesity. In this review, we will discuss in detail these studies and focus on emerging data detailing the metabolic mechanisms altering NK cells in obesity.

scholarly journals Advanced Materials and Devices for the Regulation and Study of NK Cells

2019 ◽  
Vol 20 (3) ◽  
pp. 646 ◽  
Author(s):  
Guillaume Le Saux ◽  
Mark Schvartzman
Keyword(s):  
Nk Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Advanced Materials ◽  
Immune Protection ◽  
Adaptive Responses ◽  
Environmental Signals ◽  
Recent Advances ◽  
Innate Lymphocytes

Natural Killer (NK) cells are innate lymphocytes that contribute to immune protection by cytosis, cytokine secretion, and regulation of adaptive responses of T cells. NK cells distinguish between healthy and ill cells, and generate a cytotoxic response, being cumulatively regulated by environmental signals delivered through their diverse receptors. Recent advances in biomaterials and device engineering paved the way to numerous artificial microenvironments for cells, which produce synthetic signals identical or similar to those provided by the physiological environment. In this paper, we review recent advances in materials and devices for artificial signaling, which have been applied to regulate NK cells, and systematically study the role of these signals in NK cell function.

scholarly journals Mast Cells and Natural Killer Cells—A Potentially Critical Interaction

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 514 ◽  
Author(s):  
Liliana Portales-Cervantes ◽  
Bassel Dawod ◽  
Jean S. Marshall
Keyword(s):  
Mast Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Defense ◽  
Cell Activation ◽  
Nk Cell ◽  
Mast Cell Activation ◽  
Target Cells ◽  
Effector Functions ◽  
Mucosal Surfaces

Natural killer (NK) cells play critical roles in host defense against infectious agents or neoplastic cells. NK cells provide a rapid innate immune response including the killing of target cells without the need for priming. However, activated NK cells can show improved effector functions. Mast cells are also critical for early host defense against a variety of pathogens and are predominately located at mucosal surfaces and close to blood vessels. Our group has recently shown that virus-infected mast cells selectively recruit NK cells and positively modulate their functions through mechanisms dependent on soluble mediators, such as interferons. Here, we review the possible consequences of this interaction in both host defense and pathologies involving NK cell and mast cell activation.

scholarly journals Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity

2021 ◽  
Author(s):  
James J Gilchrist ◽  
Seiko Makino ◽  
Vivek Naranbhai ◽  
Evelyn Lau ◽  
Sara Danielli ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Gene Networks ◽  
Nk Cell ◽  
Killer Cell ◽  
Regulatory Variants ◽  
Disease Associations ◽  
Trait Locus ◽  
Cell Transcriptome ◽  
Innate Lymphocytes

Natural Killer (NK) cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect NK gene expression is poorly understood. We performed expression quantitative trait locus (eQTL) mapping of negatively selected NK cells from a population of healthy Europeans (n=245). We find a significant subset of genes demonstrate eQTL specific to NK cells and these are highly informative of human disease, in particular autoimmunity. An NK cell transcriptome-wide association study (TWAS) across five common autoimmune diseases identified further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor (KIR) Region, GNLY and MC1R. Our findings provide new insights into the unique biology of NK cells, demonstrating markedly different eQTL from other immune cells, with implications for disease mechanisms.

scholarly journals Herpesvirus Evasion of Natural Killer Cells

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
Steffi De Pelsmaeker ◽  
Nicolas Romero ◽  
Massimo Vitale ◽  
Herman W. Favoreel
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Viral Infections ◽  
Nk Cell ◽  
Cell Activity ◽  
Adaptive Immune Response ◽  
Nk Cell Activity ◽  
Disease Symptoms ◽  
Adaptive Immune ◽  
Life Threatening

ABSTRACTNatural killer (NK) cells play an important role in the host response against viral infections and cancer development. They are able to kill virus-infected and tumor cells, and they produce different important cytokines that stimulate the antiviral and antitumor adaptive immune response, particularly interferon gamma. NK cells are of particular importance in herpesvirus infections, which is illustrated by systemic and life-threatening herpesvirus disease symptoms in patients with deficiencies in NK cell activity and by the myriad of reports describing herpesvirus NK cell evasion strategies. The latter is particularly obvious for cytomegaloviruses, but increasing evidence indicates that most, if not all, members of the herpesvirus family suppress NK cell activity to some extent. This review discusses the different NK cell evasion strategies described for herpesviruses and how this knowledge may translate to clinical applications.

scholarly journals Cell-intrinsic adrenergic signaling controls the adaptive NK cell response to viral infection

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Carlos Diaz-Salazar ◽  
Regina Bou-Puerto ◽  
Adriana M. Mujal ◽  
Colleen M. Lau ◽  
Madlaina von Hoesslin ◽  
...  
Keyword(s):  
Nervous System ◽  
Viral Infection ◽  
Nk Cells ◽  
Nk Cell ◽  
Clonal Expansion ◽  
Mcmv Infection ◽  
Adrenergic Signaling ◽  
Adrenergic Nervous System ◽  
Lymphocyte Responses ◽  
Innate Lymphocytes

Natural killer (NK) cells are innate lymphocytes that exhibit adaptive features, such as clonal expansion and memory, during viral infection. Although activating receptor engagement and proinflammatory cytokines are required to drive NK cell clonal expansion, additional stimulatory signals controlling their proliferation remain to be discovered. Here, we describe one such signal that is provided by the adrenergic nervous system, and demonstrate that cell-intrinsic adrenergic signaling is required for optimal adaptive NK cell responses. Early during mouse cytomegalovirus (MCMV) infection, NK cells up-regulated Adrb2 (which encodes the β2-adrenergic receptor), a process dependent on IL-12 and STAT4 signaling. NK cell–specific deletion of Adrb2 resulted in impaired NK cell expansion and memory during MCMV challenge, in part due to a diminished proliferative capacity. As a result, NK cell-intrinsic adrenergic signaling was required for protection against MCMV. Taken together, we propose a novel role for the adrenergic nervous system in regulating circulating lymphocyte responses to viral infection.

scholarly journals Role of Natural Killer Cells in Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3694
Author(s):  
Asad Javed ◽  
Mohammed Milhem
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Uveal Melanoma ◽  
Nk Cell ◽  
Immune Therapy ◽  
Adaptive Responses ◽  
Barriers To Success ◽  
Liver Sinusoids ◽  
Immune Tolerant

Uveal melanoma has a high mortality rate following metastasis to the liver. Despite advances in systemic immune therapy, treatment of metastatic uveal melanoma (MUM) has failed to achieve long term durable responses. Barriers to success with immune therapy include the immune regulatory nature of uveal melanoma as well as the immune tolerant environment of the liver. To adequately harness the anti-tumor potential of the immune system, non-T cell-based approaches need to be explored. Natural Killer (NK) cells possess potent ability to target tumor cells via innate and adaptive responses. In this review, we discuss evidence that highlights the role of NK cell surveillance and targeting of uveal melanoma. We also discuss the repertoire of intra-hepatic NK cells. The human liver has a vast and diverse lymphoid population and NK cells comprise 50% of the hepatic lymphocytes. Hepatic NK cells share a common niche with uveal melanoma micro-metastasis within the liver sinusoids. It is, therefore, crucial to understand and investigate the role of intra-hepatic NK cells in the control or progression of MUM.

scholarly journals The Effect of Antiretroviral Naïve HIV-1 Infection on the Ability of Natural Killer Cells to Produce IFN-γ upon Exposure to Plasmodium falciparum-Infected Erythrocytes

2017 ◽  
Vol 2 (1) ◽  
pp. 1-13
Author(s):  
Carole Stéphanie Sake ◽  
Loveline Ngu ◽  
Georgia Ambada ◽  
Jean Paul Chedjou ◽  
Nadesh Nji ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Plasmodium Species ◽  
Sub Saharan Africa ◽  
Cell Mediated Immunity ◽  
Infected People ◽  
Ifn Γ ◽  
Hiv 1

Background: In sub-Saharan Africa, intense perennial Plasmodium species transmission coincides with areas of high prevalence of the human immunodeficiency virus type 1 (HIV) infection. This implies that antiretroviral naïve HIV-infected people living within these regions are repeatedly exposed to Plasmodium species infection and consequently malaria. Natural killer (NK) cells are known to contribute to malaria immunity through the production of IFN-γ after exposure to Plasmodium falciparum-infected erythrocytes (infected red blood cells [iRBC]). However, in antiretroviral naïve HIV-1 infection, these functions could be impaired. In this study we assess the ability of NK cells from antiretroviral naïve HIV-1-infected people to respond to iRBC. Method: Magnetically sorted NK cells from antiretroviral naïve HIV-1-infected people were tested for their ability to respond to iRBC following in vitro coculture. NK cell IFN-γ production after coculture was measured through multiparametric flow cytometry analysis. Results: Our data show a significant reduction (p = 0.03) in IFN-γ production by NK cells from antiretroviral naïve HIV-1-infected people after coculture with iRBCs. This was in contrast to the NK cell response from healthy controls, which demonstrated elevated IFN-γ production. NK cell IFN-γ production from untreated HIV-1-infected participants correlated inversely with the viral load (r = -0.5, p = 0.02) and positively with total helper CD4+ T-cell count (r = 0.4, p = 0.04). Thus, antiretroviral naïve HIV-1 infection can dampen NK cell-mediated immunity to P. falciparum infection in malaria-intense regions. This could in effect escalate morbidity and mortality in people chronically infected with HIV-1.

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