scholarly journals NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients

2016 ◽  
Vol 197 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Caterina Lapenta ◽  
Simona Donati ◽  
Francesca Spadaro ◽  
Paolo Castaldo ◽  
Filippo Belardelli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Follicular Lymphoma ◽  
Cell Activation ◽  
Nk Cell ◽  
Apoptotic Cells ◽  
Antitumor Response

scholarly journals Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Vivian Vasconcelos Costa ◽  
Weijian Ye ◽  
Qingfeng Chen ◽  
Mauro Martins Teixeira ◽  
Peter Preiser ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Virus Infection ◽  
Dengue Virus ◽  
Nk Cells ◽  
Adhesion Molecules ◽  
Cell Activation ◽  
Nk Cell ◽  
Denv Infection ◽  
Ifn Γ

ABSTRACT Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo, identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection.

Natural-killer cells and dendritic cells: “l'union fait la force”

Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2252-2258 ◽  
Author(s):  
Thierry Walzer ◽  
Marc Dalod ◽  
Scott H. Robbins ◽  
Laurence Zitvogel ◽  
Eric Vivier
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Activation ◽  
Nk Cell ◽  
Interleukin 12 ◽  
Cell Contact ◽  
Ifn Γ

AbstractSeveral recent publications have focused on the newly described interactions between natural-killer (NK) cells and dendritic cells (DCs). Activated NK cells induce DC maturation either directly or in synergy with suboptimal levels of microbial signals. Immature DCs appear susceptible to autologous NK-cell-mediated cytolysis while mature DCs are protected. NK-cell-induced DC activation is dependent on both tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) secretion and a cell-cell contact involving NKp30. In vitro, interleukin-12 (IL-12)/IL-18, IL-15, and IFN-α/β production by activated DCs enhance, in turn, NK-cell IFN-γ production, proliferation, and cytotoxic potential, respectively. In vivo, NK-cell/DC interactions may occur in lymphoid organs as well as in nonlymphoid tissues, and their consequences are multiple. By inducing DC activation, NK-cell activation induced by tumor cells can indirectly promote antitumoral T-cell responses. Reciprocally, DCs activated through Toll-like receptors (TLRs) induce potent NK-cell activation in antiviral responses. Thus, DCs and NK cells are equipped with complementary sets of receptors that allow the recognition of various pathogenic agents, emphasizing the role of NK-cell/DC crosstalk in the coordination of innate and adaptive immune responses.

Intravenous immunoglobulins suppress T-cell priming by modulating the bidirectional interaction between dendritic cells and natural killer cells

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3253-3262 ◽  
Author(s):  
Thanyalak Tha-In ◽  
Herold J. Metselaar ◽  
Hugo W. Tilanus ◽  
Zwier M. A. Groothuismink ◽  
Ernst J. Kuipers ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Nk Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Intravenous Immunoglobulins ◽  
Interferon Γ ◽  
T Cell Priming ◽  
Induced Apoptosis

AbstractThe modes of action of intravenous immunoglobulins (IVIgs) in exerting their immunomodulatory properties are broad and not fully understood. IVIgs can modulate the function of various immune cells, including suppressing the capacity of dendritic cells (DCs) to stimulate T cells. In the present study, we showed that DCs matured in the presence of IVIgs (IVIg-DCs) activated NK cells, and increased their interferon-γ production and degranulation. The activated NK cells induced apoptosis of the majority of IVIg-DCs. In consequence, only in the presence of NK cells, IVIg-DCs were 4-fold impaired in their T-cell priming capacity. This was due to NK-cell–mediated antibody-dependent cellular cytotoxicity (ADCC) to IVIg-DCs, probably induced by IgG multimers, which could be abrogated by blockade of CD16 on NK cells. Furthermore, IVIg-DCs down-regulated the expression of NKp30 and KIR receptors, and induced the generation of CD56brightCD16−CCR7+ lymph node–type NK cells. Our results identify a novel pathway, in which IVIgs induce ADCC of mature DCs by NK cells, which downsizes the antigen-presenting pool and inhibits T-cell priming. By influencing the interaction between DCs and NK cells, IVIgs modulate the ability of the innate immunity to trigger T-cell activation, a mechanism that can “cool down” the immune system at times of activation.

scholarly journals Vaccination with Live Leishmania major and CpG DNA Promotes Interleukin-2 Production by Dermal Dendritic Cells and NK Cell Activation

2009 ◽  
Vol 16 (11) ◽  
pp. 1601-1606 ◽  
Author(s):  
Eva Maria Laabs ◽  
Wenhui Wu ◽  
Susana Mendez
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Cell Activation ◽  
Leishmania Major ◽  
Nk Cell ◽  
Natural Infection ◽  
Interleukin 2 ◽  
Innate Immune Responses ◽  
Cpg Dna ◽  
Ifn Γ

ABSTRACT Cutaneous leishmaniasis due to Leishmania major is an emerging, chronic parasitic disease that causes disfigurement and social stigmatization. Drug therapy is inadequate, and there is no vaccine. Inoculation of virulent parasites (leishmanization) is the only intervention that has ever provided protection, because it mimics natural infection and immunity, but it was discontinued due to safety concerns (uncontrolled vaccinal lesions). In an effort to retain the benefits (immunity) while avoiding the side effects (lesions) of leishmanization, we immunized C57BL/6 mice with L. major and CpG DNA (Lm/CpG). This combination prevented lesions while inducing immunity. Also, the vaccination with live parasites and the Toll-like receptor 9 agonist enhanced innate immune responses by activating dermal dendritic cells (DCs) to produce cytokines. Here we report that the Lm/CpG vaccine induced dermal DCs, but not bone marrow-derived DCs, to produce interleukin-2 (IL-2). The release of this unusual DC-derived cytokine was concomitant with a peak in numbers of NK cells that produced gamma interferon (IFN-γ) and also enhanced activation of proliferation of IFN-γ+ CD4+ T cells. Parasite growth was controlled in Lm/CpG-vaccinated animals. This is the first demonstration of the ability of dermal DCs to produce IL-2 and of the activation of NK cells by vaccination in the context of leishmaniasis. Understanding how the Lm/CpG vaccine enhances innate immunity may provide new tools to develop vaccines against L. major, other chronic infectious diseases, or other conditions, such as cancer.

Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2554-2561 ◽  
Author(s):  
Dominique Valteau-Couanet ◽  
Christophe Leboulaire ◽  
Kim Maincent ◽  
Muriel Tournier ◽  
Olivier Hartmann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Peripheral Blood Stem Cells ◽  
Term Survival ◽  
Effector Functions ◽  
Cell Functions

Natural killer (NK)/lymphokine-activated killer (LAK) cell-based immunotherapy could be beneficial against major histocompatibility complex class I–negative tumor residual disease such as neuroblastoma (NB), provided that interleukin 2 (IL-2) or surrogate nontoxic NK cell stimulatory factors could sustain NK cell activation and survival in vivo. Here we show that human monocyte–derived dendritic cells (MD-DCs) promote potent NK/LAK effector functions and long-term survival, circumventing the need for IL-2. This study demonstrates (1) the feasibility of differentiating granulocyte colony-stimulating factor–mobilized hematopoietic peripheral blood stem cells (PBSCs) into high numbers of functional MD-DCs and NK/LAK cells in a series of 12 children with stage 4 neuroblastoma (NB); (2) potent DC-mediated NK cell activation in autologous settings; (3) the reciprocal capacity of NK/LAK cells to turn immature DCs into maturing cells electively capable of triggering NK cell functions; and (4) the unique capacity of maturing DCs to sustain NK cell survival, superior to that achieved in IL-2. These data show a reciprocal interaction between DCs and NK/LAK cells, leading to the amplification of NK cell effector functions, and support the implementation of DC/NK cell–based immunotherapy for purging the graft and/or controlling minimal residual disease after autologous stem cell transplantation.

scholarly journals Virally infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15

Blood ◽  
2010 ◽  
Vol 116 (4) ◽  
pp. 575-583 ◽  
Author(s):  
Lazar Vujanovic ◽  
David E. Szymkowski ◽  
Sean Alber ◽  
Simon C. Watkins ◽  
Nikola L. Vujanovic ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Activation ◽  
Nk Cell ◽  
Recombinant Adenovirus ◽  
Interferon Γ ◽  
Cell Contact ◽  
Immune Functions ◽  
Cd69 Expression

Abstract Recombinant adenovirus-engineered dendritic cells (Ad.DCs) are potent immunologic adjuvants of antiviral and anticancer vaccines. The effectiveness of Ad.DC-based vaccines may depend on the ability of Ad.DCs to crosstalk with natural killer (NK) cells and to activate, polarize, and bridge innate and adaptive immunity. We investigated, for the first time, whether and how human Ad.DCs activate NK cells, and compared the Ad.DC function with that of immature DCs and matured DCs (mDCs). We found that adenovirus transduction and lipopolysaccharide/interferon-γ-induced maturation increased expression of transmembrane tumor necrosis factor (TNF) and trans-presented (trans) interleukin-15 (IL-15) on DCs, leading to enhanced NK cell activation without enhancing DC susceptibility to NK cell-mediated killing. This crosstalk enhanced NK cell CD69 expression, interferon-γ secretion, proliferation, and antitumor activities, with Ad.DCs being significantly more effective than immature DCs, but less effective than mDCs. The Ad.DC and mDC crosstalk with NK cells was largely prevented by physical separation of DCs and NK cells, and neutralization of total TNF and IL-15, but not by selective sequestration of soluble TNF. These findings demonstrate that both Ad.DCs and mDCs can efficiently promote innate immune functions by activation of NK cells through the cooperative activities of tmTNF and trans-IL-15 mediated by cell-to-cell contact.

Adenovirus type 35, but not type 5, stimulates NK cell activation via plasmacytoid dendritic cells and TLR9 signaling

2012 ◽  
Vol 51 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Jens H.W. Pahl ◽  
Dirk H.J. Verhoeven ◽  
Kitty M.C. Kwappenberg ◽  
Jort Vellinga ◽  
Arjan C. Lankester ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Adenovirus Type ◽  
Plasmacytoid Dendritic Cells ◽  
Tlr9 Signaling

scholarly journals NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection

2007 ◽  
Vol 178 (5) ◽  
pp. 2688-2698 ◽  
Author(s):  
Monia Draghi ◽  
Achal Pashine ◽  
Bharati Sanjanwala ◽  
Ketevan Gendzekhadze ◽  
Claudia Cantoni ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
Influenza Infection ◽  
Human Response
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