The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44)

2003 ◽  
Vol 33 (9) ◽  
pp. 2410-2418 ◽  
Author(s):  
Andrea De Maria ◽  
Manuela Fogli ◽  
Paola Costa ◽  
Giuseppe Murdaca ◽  
Francesco Puppo ◽  
...  
Keyword(s):  
Nk Cell ◽  
Surface Expression ◽  
Natural Cytotoxicity ◽  
Cytolytic Function ◽  
Natural Cytotoxicity Receptors ◽  
Hiv 1 ◽  
Reduced Surface

scholarly journals Influenza A Virus Hemagglutinin and Other Pathogen Glycoprotein Interactions with NK Cell Natural Cytotoxicity Receptors NKp46, NKp44, and NKp30

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 156
Author(s):  
Jasmina M. Luczo ◽  
Sydney L. Ronzulli ◽  
Stephen M. Tompkins
Keyword(s):  
Influenza Virus ◽  
Nk Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Nk Cell ◽  
Influenza Virus Infection ◽  
Target Cells ◽  
Natural Cytotoxicity ◽  
Activating Receptors ◽  
Natural Cytotoxicity Receptors

Natural killer (NK) cells are part of the innate immunity repertoire, and function in the recognition and destruction of tumorigenic and pathogen-infected cells. Engagement of NK cell activating receptors can lead to functional activation of NK cells, resulting in lysis of target cells. NK cell activating receptors specific for non-major histocompatibility complex ligands are NKp46, NKp44, NKp30, NKG2D, and CD16 (also known as FcγRIII). The natural cytotoxicity receptors (NCRs), NKp46, NKp44, and NKp30, have been implicated in functional activation of NK cells following influenza virus infection via binding with influenza virus hemagglutinin (HA). In this review we describe NK cell and influenza A virus biology, and the interactions of influenza A virus HA and other pathogen lectins with NK cell natural cytotoxicity receptors (NCRs). We review concepts which intersect viral immunology, traditional virology and glycobiology to provide insights into the interactions between influenza virus HA and the NCRs. Furthermore, we provide expert opinion on future directions that would provide insights into currently unanswered questions.

scholarly journals Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors

2004 ◽  
Vol 34 (4) ◽  
pp. 961-971 ◽  
Author(s):  
Pascale André ◽  
Roberta Castriconi ◽  
Marion Espéli ◽  
Nicolas Anfossi ◽  
Tiffany Juarez ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Cell Activation ◽  
Nk Cell ◽  
Natural Cytotoxicity ◽  
Natural Cytotoxicity Receptors

scholarly journals CD59 is physically and functionally associated with natural cytotoxicity receptors and activates human NK cell-mediated cytotoxicity

2003 ◽  
Vol 33 (12) ◽  
pp. 3367-3376 ◽  
Author(s):  
Emanuela Marcenaro ◽  
Raffaella Augugliaro ◽  
Michela Falco ◽  
Roberta Castriconi ◽  
Silvia Parolini ◽  
...  
Keyword(s):  
Nk Cell ◽  
Natural Cytotoxicity ◽  
Natural Cytotoxicity Receptors

scholarly journals HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell–mediated killing

Blood ◽  
2010 ◽  
Vol 115 (7) ◽  
pp. 1354-1363 ◽  
Author(s):  
Jonathan Richard ◽  
Sardar Sindhu ◽  
Tram N. Q. Pham ◽  
Jean-Philippe Belzile ◽  
Éric A. Cohen
Keyword(s):  
Dna Damage ◽  
Cell Surface ◽  
Nk Cell ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Target Cells ◽  
Nkg2d Ligands ◽  
Infected Cells ◽  
Nkg2d Receptor ◽  
Hiv 1

AbstractHIV up-regulates cell-surface expression of specific ligands for the activating NKG2D receptor, including ULBP-1, -2, and -3, but not MICA or MICB, in infected cells both in vitro and in vivo. However, the viral factor(s) involved in NKG2D ligand expression still remains undefined. HIV-1 Vpr activates the DNA damage/stress-sensing ATR kinase and promotes G2 cell-cycle arrest, conditions known to up-regulate NKG2D ligands. We report here that HIV-1 selectively induces cell-surface expression of ULBP-2 in primary CD4+ T lymphocytes by a process that is Vpr dependent. Importantly, Vpr enhanced the susceptibility of HIV-1–infected cells to NK cell–mediated killing. Strikingly, Vpr alone was sufficient to up-regulate expression of all NKG2D ligands and thus promoted efficient NKG2D-dependent NK cell–mediated killing. Delivery of virion-associated Vpr via defective HIV-1 particles induced analogous biologic effects in noninfected target cells, suggesting that Vpr may act similarly beyond infected cells. All these activities relied on Vpr ability to activate the ATR-mediated DNA damage/stress checkpoint. Overall, these results indicate that Vpr is a key determinant responsible for HIV-1–induced up-regulation of NKG2D ligands and further suggest an immunomodulatory role for Vpr that may not only contribute to HIV-1–induced CD4+ T-lymphocyte depletion but may also take part in HIV-1–induced NK-cell dysfunction.

scholarly journals Human NK cell recognition of target cells in the prism of natural cytotoxicity receptors and their ligands

2012 ◽  
Vol 9 (3) ◽  
pp. 267-274 ◽  
Author(s):  
Michael Brusilovsky ◽  
Benyamin Rosental ◽  
Avishai Shemesh ◽  
Michael Y. Appel ◽  
Angel Porgador
Keyword(s):  
Nk Cell ◽  
Target Cells ◽  
Cell Recognition ◽  
Natural Cytotoxicity ◽  
Natural Cytotoxicity Receptors ◽  
Nk Cell Recognition

scholarly journals Altered Expression of Natural Cytotoxicity Receptors and NKG2D on Peripheral Blood NK Cell Subsets in Breast Cancer Patients

2016 ◽  
Vol 9 (5) ◽  
pp. 384-391 ◽  
Author(s):  
Nayeli Goreti Nieto-Velázquez ◽  
Yessica Dorin Torres-Ramos ◽  
José Luis Muñoz-Sánchez ◽  
Lorena Espinosa-Godoy ◽  
Susana Gómez-Cortés ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Natural Cytotoxicity ◽  
Altered Expression ◽  
Natural Cytotoxicity Receptors

Umbilical Cord Blood T Cells Express the Natural Cytotoxicity Receptors, NKp30, NKp44 and NKp46 after IL-15 Stimulation, but Only NKp30 Is Functional.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 61-61
Author(s):  
Qin Tang ◽  
Bartosz Grzywacz ◽  
Hongbo Wang ◽  
Nandini Kataria ◽  
John E. Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Nk Cell ◽  
Natural Cytotoxicity ◽  
Nk Cell Receptors ◽  
Natural Cytotoxicity Receptors ◽  
Dose Dependent

Abstract The natural cytotoxicity receptors (NCRs), NKp30, NKp44 and NKp46, are a recently identified group of receptors that play a central role in NK cell killing of malignant cells. Previous studies show that the NCRs are restricted to the NK cell lineage. However, we noted that a small fraction of freshly isolated umbilical cord blood (UCB) T cells expressed NKp30 (1.7±0.9%, n=8), but not NKp44 (0.4±0.4%, n=8) or NKp46 (0.5±0.4%, n=8). Thus, we investigated whether NCRs could be induced on either UCB or adult peripheral blood (PB) T cells after culture in IL-15 for 14 days. This cytokine was chosen since previous studies show that IL-15 induces other NK cell receptors on both UCB and PB T cells. Surprisingly, UCB, but not PB T cells, acquired NKp30 (37±10% vs 4±2%, p=0.01), NKp44 (41±20% vs. 1±0.6%, p=0.01) and NKp46 (13±7% vs 0.6±0.5%, p=0.01). NCRs were found mainly on CD8+ or CD3+CD56+ UCB T cells. Further studies addressed whether other cytokines could induce NCR expression on UCB T cells. Both IL-2 and IL-15 showed a dose dependent induction of NCRs. In contrast, IL-7 induced only NKp30 on UCB T cells, but in a non-dose dependent manner. IL-4 abrogated NCR expression, even in the presence of IL-15. Considering that the ligands for the NCRs are not yet elucidated, we performed functional studies using agonist mAbs and NK cells served as controls. Surprisingly, while all three NCRs were expressed on IL-15 expanded UCB T cells, only NKp30 was functional as demonstrated by degranulation (CD107a), IFN-γ release, and redirected killing assays (reverse ADCC). Previous studies show that the NKp30, −44 and −46 cooperate to induce NK killing. However, the simultaneous triggering of all 3 NCRs did not increase UCB T cell cytotoxicity. Some NK cell receptors modulate TCR triggering, but this was not the case with NCRs. We did find that another NK cell receptor, NKG2D, enhanced the cytoxic triggering of NKp30, but not other NCRs. To address the lack of function of NKp44 and −46 on UCB T cells, the expression of adapter proteins required for signaling through these receptors were determined. The proximal receptor for NKp44 signaling, DAP12, was absent in UCB T cells. Thus, the lack of DAP12 likely explains the absence of NKp44 signaling. Both of the adapters used by NKp30 and −46 (FcεR1γ and CD3ζ) were detected. As stated above, NKp46 was expressed on significantly fewer cells than NKp30 (13±7% vs 37±10%) and this likely accounts for the lack of NKp46 function. Considering that UCB contains mostly naive T cells, we hypothesized that PB naive T cells may also acquire NCRs. To test this, PB T cell subsets (naive, central memory and effector memory) were FACS sorted and cultured for 14 days in IL-15. NKp30 was induced on a small number of naive, but not memory PB T cells. Unlike UCB T cells, NKp30 on naive PB T cells was non-functional. PB T cells lacked FcεR1γ, while UCB T cells expressed it, suggesting that this adapter protein is critical for NKp30 signaling. Collectively, these results show that UCB T cells are unique in their ability to acquire NCRs. Moreover, only NKp30 is functional. The lack of function of NKp44 and -46 is due to the absence of DAP12 and the low level of NKp46 expression, respectively. Lastly, while some naive PB T cells can acquire NKp30, it is not functional due to the lack of FcεR1γ. Such studies highlight the differences between UCB and PB T cells and challenge the dogma that NCRs are NK cell specific.

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