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Natural killers

Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
John P Veluchamy, A Marijne Heeren, Jan Spanholtz, Jaap D H van Eendenburg, Daniëlle A M Heideman, Gemma G Kenter, Henk M Verheul, Hans J van der Vliet, Ekaterina S Jordanova, Tanja D de Gruijl
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK)...
October 25, 2016: Cancer Immunology, Immunotherapy: CII
Sara De Biasi, Elena Bianchini, Milena Nasi, Margherita Digaetano, Lara Gibellini, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Marcello Pinti, Cristina Mussini, Andrea Cossarizza
INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients. METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR)...
November 13, 2016: AIDS
Paola Triggianese, Paola Conigliaro, Maria Sole Chimenti, Livia Biancone, Giovanni Monteleone, Roberto Perricone, Ivan Monteleone
OBJECTIVES: Both the innate and the adaptive immune responses contribute to the onset of chronic inflammation in spondyloarthritis (SpA). The association between SpA and inflammatory bowel disease (IBD, enteropathic SpA-ESpA) has been largely established and suggests a shared pathophysiology. There is evidence that innate lymphoid cells (ILC) are involved in the pathogenesis of both SpA and IBD while no evidence has been reported to date on ESpA. We aimed to analyse for the first time the frequency and cytokine expression of ILC in peripheral blood from ESpA patients compared with both IBD and healthy subjects...
October 21, 2016: Clinical and Experimental Rheumatology
Paolo Lissoni
Despite its apparent failure in cancer therapy, IL-2 still remains fundamental in the activation of antitumor immunity. Areas covered: The aim of this review is the reinterpretation of the role of IL-2 in anticancer immunity, according to knowledge gained of the cytokine network, by highlighting its importance in inducing T helper-1 (TH1) cell proliferation, natural killer (NK) actHivation and IL-12 secretion. However, its main negative effect is the stimulation of regulatory T cells (Tregs), which in contrast suppresses anticancer immunity...
October 26, 2016: Expert Review of Clinical Immunology
Tai-Na Wu, Kun-Hsien Lin, Ying-Ta Wu, Jing-Rong Huang, Jung-Tung Hung, Jen-Chine Wu, Chien-Yu Chen, Kuo-Ching Chu, Nan-Horng Lin, Alice L Yu, Chi-Huey Wong
Glycosphingolipids (GSLs) bearing the α-galactosyl head group and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) to stimulate both murine and human invariant natural killer T (iNKT) cells and to induce antibody isotope switch to IgG. In this study, we replaced the galactosyl group with glucose (αGlc) and its fluoro-analogs, and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal in stimulating human iNKT cells but weaker in mice...
October 26, 2016: ACS Chemical Biology
Pedro Berraondo, Luna Minute, Daniel Ajona, Leticia Corrales, Ignacio Melero, Ruben Pio
Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors...
November 2016: Immunological Reviews
Belen Rubio-Gonzalez, Jasmine Zain, Steven T Rosen, Christiane Querfeld
The primary cutaneous lymphomas are a heterogeneous group of T-, Natural Killer- and B- cell neoplasms with a wide range of clinical and pathological presentations, and with very different prognoses compared to systemic lymphomas. Recent studies have shown that the skin microenvironment, which is composed of various immune cell subsets as well as their spatial distribution and T-cell interactions through different chemokines and cytokines, has an important role in the development and pathogenesis of cutaneous lymphomas and has assisted in the development of novel and more effective immunotherapies...
October 26, 2016: British Journal of Haematology
Yang Yu, Yan Liu, Chen Zong, Qingbo Yu, Xue Yang, Lei Liang, Fei Ye, Li Nong, Yuxian Jia, Yongkui Lu, Zhipeng Han
Mesenchymal stem cells (MSCs) are generally used in regenerative medicine, tissue engineering and therapy for immune disorder diseases. However, due to the immunosuppressive function of MSCs, the application of MSCs in breast cancer therapy remains limited. Sirt1 is the closest mammalian homologue of the yeast enzyme Sir2 which has an established capacity to influence yeast replicative lifespan. In this study, we demonstrated the effect of MSCs with Sirt1 overexpression (MSCs-Sirt1) in mice bearing 4T1 breast cancer and investigated the underlying mechanism...
October 26, 2016: Scientific Reports
Vivien Béziat, Hugo Hilton, Paul J Norman, James A Traherne
Killer-cell immunoglobulin-like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. Firstly, they contribute to host immune response, both innate and adaptive, through their expression by natural killer (NK) cells and T cells. Secondly, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their HLA class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, which are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions...
October 25, 2016: Immunology
Lun Cai, Lei Yu, Sa Liu, Tongxun Li, Xiaoping Zhang, Wei Cui, Jie Du, Qinyi Zhang
Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n = 18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8- NKT cell subsets (8...
October 24, 2016: Inflammation
June Ho Shin, Mikel D Haggadone, John B Sunwoo
The Distal-less (Dlx) homeobox transcription factors (TFs) play a prominent role in regulating multiple facets of vertebrate biology. Though widely studied as mediators of tissue development, recent work has uncovered a role for this TF family in modulating the vertebrate hematopoietic compartment. Pertinent to our study, murine Dlx1-3 are expressed in an innate lymphocyte population known as natural killer (NK) cells, and they are implicated to assume a functional role in the NK cell maturation pathway. However, Dlx target genes are poorly understood...
September 2016: Biochemistry and Biophysics Reports
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
Karin Hock, Johannes Laengle, Irina Kuznetsova, Andrej Egorov, Balazs Hegedus, Balazs Dome, Thomas Wekerle, Monika Sachet, Michael Bergmann
BACKGROUND: Interleukin-15 has become a promising molecule in the context of eliciting an effective, antitumor immune response because it is able to stimulate cells of the innate and adaptive immune system. METHODS: We generated an interleukin-15-expressing oncolytic influenza A virus for the treatment of an established murine tumor model. RESULTS: Our oncolytic influenza A virus produced large amounts of interleukin-15 and induced proliferation and activation of human T cells in vitro...
October 21, 2016: Surgery
Elisabeth Salzer, Deniz Cagdas, Miroslav Hons, Emily M Mace, Wojciech Garncarz, Özlem Yüce Petronczki, René Platzer, Laurène Pfajfer, Ivan Bilic, Sol A Ban, Katharina L Willmann, Malini Mukherjee, Verena Supper, Hsiang Ting Hsu, Pinaki P Banerjee, Papiya Sinha, Fabienne McClanahan, Gerhard J Zlabinger, Winfried F Pickl, John G Gribben, Hannes Stockinger, Keiryn L Bennett, Johannes B Huppa, Loïc Dupré, Özden Sanal, Ulrich Jäger, Michael Sixt, Ilhan Tezcan, Jordan S Orange, Kaan Boztug
RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1...
October 24, 2016: Nature Immunology
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Mazen Al-Hommrani, Paramita Chakraborty, Shilpak Chatterjee, Shikhar Mehrotra
Cell, the basic unit of life depends for its survival on nutrients and thereby energy to perform its physiological function. Cells of lymphoid and myeloid origin are key in evoking an immune response against "self" or "non-self" antigens. The thymus derived lymphoid cells called T cells are a heterogenous group with distinct phenotypic and molecular signatures that have been shown to respond against an infection (bacterial, viral, protozoan) or cancer. Recent studies have unearthed the key differences in energy metabolism between the various T cell subsets, natural killer cells, dendritic cells, macrophages and myeloid derived suppressor cells...
2016: J Immunol Res Ther
Aiko Tanaka, Mie Nishimura, Yuji Sato, Hiroki Sato, Jun Nishihira
Pleurotus cornucopiae (Oyster mushroom, Tamogitake) has long been eaten as a functional food for enhancement of the immune system, but its effectiveness has not been well confirmed in humans. To this end, we set up a double-blind placebo-controlled human clinical trial to investigate the potential of Oyster mushrooms with respect to the up-regulation of the immune system. The subjects ingested Oyster mushroom extract for 8 weeks. We measured the serum cytokine levels involved in regulation of the immune system, including interferon (IFN)-γ, interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, and tumor-necrosis factor (TNF)-α...
October 2016: Journal of Traditional and Complementary Medicine
Todd A Fehniger, Megan A Cooper
Due to their ability to kill cancer cells and produce proinflammatory cytokines, natural killer (NK) cells have long been of clinical interest for their antitumor properties. The recent discovery of NK cell memory demonstrates that NK cell functions, and potentially antitumor responses, can be enhanced long term. Following nonspecific activation with the cytokines IL-12, IL-15, and IL-18 or in response to antigens or cytomegalovirus (CMV), human and mouse NK cells exhibit stable, enhanced functional responses with phenotypic and molecular changes...
October 20, 2016: Trends in Immunology
G Kamkamidze, M Butsashvili, K Gendzekhadze
Hepatitis C virus (HCV) infection remains one of the most important blood-borne diseases worldwide with about 130-170 million people chronically infected with hepatitis C virus, and more than 350 000 people die from hepatitis C-related liver diseases each year. Infection with HCV becomes chronic in approximately 80% of cases, while in up to 20% of cases hepatitis C virus is cleared from the human organism. Chronic infections of hepatitis C often leads to the end-stage liver diseases such as cirrhosis and hepatocellular carcinoma...
September 2016: Georgian Medical News
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