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https://www.readbyqxmd.com/read/28820897/persistent-infection-due-to-a-small-colony-variant-of-burkholderia-pseudomallei-leads-to-pd-1-upregulation-on-circulating-immune-cells-and-mononuclear-infiltration-in-viscera-of-experimental-balb-c-mice
#1
Jia-Xiang See, Samudi Chandramathi, Mahmood Ameen Abdulla, Jamuna Vadivelu, Esaki M Shankar
BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28815219/conventional-nk-cells-and-ilc1-are-partially-ablated-in-the-livers-of-ncr1-icre-tbx21-fl-fl-mice
#2
Antonia O Cuff, Victoria Male
Mouse liver contains both Eomes-dependent conventional natural killer (cNK) cells and Tbet-dependent liver-resident type I innate lymphoid cells (ILC1). In order to better understand the role of ILC1, we attempted to generate mice that would lack liver ILC1, while retaining cNK, by conditional deletion of Tbet in NKp46+ cells. Here we report that the Ncr1 (iCre)Tbx21 (fl/fl) mouse has a roughly equivalent reduction in both the cNK and ILC1 compartments of the liver, limiting its utility for investigating the relative contributions of these two cell types in disease models...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#3
H M Kim, R Lee, E S Lee, M H Kwon, J H Huh, B-E Kwon, E-K Park, S-Y Chang, M-N Kweon, P-H Kim, H-J Ko, C H Chung
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease, and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism...
August 16, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28803951/monocytes-inhibit-hepatitis-c-virus-induced-trail-expression-on-cd56-bright-nk-cells
#4
Dalila Mele, Stefania Mantovani, Barbara Oliviero, Giulia Grossi, Andrea Lombardi, Mario U Mondelli, Stefania Varchetta
BACKGROUND AND AIMS: Natural killer (NK) cells play an important role in the pathogenesis of HCV infection. We have previously shown that culture-derived HCV (HCVcc) enhance tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) expression on healthy but not on HCV-infected patient-derived NK cells, which was likely dependent on accessory cells. Here we sought mechanistic insights involved in altered TRAIL upregulation in this setting. METHODS: Peripheral blood mononuclear cells (PBMC) from controls and HCV-infected patients were exposed to HCVcc...
August 10, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28802693/diversity-of-tissue-resident-nk-cells
#5
REVIEW
Hui Peng, Zhigang Tian
Although natural killer (NK) cells were initially named for their spontaneous tumor-killing capacity, their concept has been greatly expanded with more than 40 years of extensive investigation. Currently, NK cells are known as a heterogeneous population of innate lymphoid cell (ILC) family, consisting of different subsets with unique phenotypic and functional features. Recent studies have shown that tissue-resident NK (trNK) cells, which are distinct from conventional NK (cNK) cells, preferentially distribute in non-lymphoid tissues, such as the liver, uterus, salivary gland, and adipose...
August 9, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28792982/proliferative-capacity-exhibited-by-human-liver-resident-cd49a-cd25-nk-cells
#6
Glòria Martrus, Tobias Kautz, Sebastian Lunemann, Laura Richert, Laura Glau, Wilhelm Salzberger, Hanna Goebels, Annika Langeneckert, Leonard Hess, Tobias Poch, Christoph Schramm, Karl J Oldhafer, Martina Koch, Eva Tolosa, Björn Nashan, Marcus Altfeld
The recruitment and retention of Natural Killer (NK) cells in the liver are thought to play an important role during hepatotropic infections and liver cirrhosis. The aims of this study were to determine differences between liver-derived and peripheral blood-derived NK cells in the context of liver inflammation and cirrhosis. We conducted a prospective dual-center cross-sectional study in patients undergoing liver transplantation or tumor-free liver resections, in which both liver tissue and peripheral blood samples were obtained from each consenting study participants...
2017: PloS One
https://www.readbyqxmd.com/read/28780700/natural-killer-cells-in-hepatocellular-carcinoma-current-status-and-perspectives-for-future-immunotherapeutic-approaches
#7
REVIEW
Min Yu, Zonghai Li
Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third leading cause of cancer-related mortalities worldwide. In the last few years, treatments for HCC have significantly improved from a mere surgical resection to a series of minimally invasive therapies and targeted drugs. However, recurrence frequently occurs even upon curative therapeutics, and drug therapies generally produce disappointing results, with the overall prognosis dismal. This challenging clinical scenario warrants new effective and life-prolonging strategies for patients with HCC...
August 5, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28765218/dengue-virus-infected-dendritic-cells-but-not-monocytes-activate-natural-killer-cells-through-a-contact-dependent-mechanism-involving-adhesion-molecules
#8
Vivian Vasconcelos Costa, Weijian Ye, Qingfeng Chen, Mauro Martins Teixeira, Peter Preiser, Eng Eong Ooi, Jianzhu Chen
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...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28751776/hobit-expression-by-a-subset-of-human-liver-resident-cd56-bright-natural-killer-cells
#9
Sebastian Lunemann, Gloria Martrus, Hanna Goebels, Tobias Kautz, Annika Langeneckert, Wilhelm Salzberger, Martina Koch, Madeleine J Bunders, Björn Nashan, Klaas P J M van Gisbergen, Marcus Altfeld
Immune responses show a high degree of tissue specificity shaped by factors influencing tissue egress and retention of immune cells. The transcription factor Hobit was recently shown to regulate tissue-residency in mice. Whether Hobit acts in a similar capacity in humans remains unknown. Our aim was to assess the expression and contribution of Hobit to tissue-residency of Natural Killer (NK) cells in the human liver. The human liver was enriched for CD56(bright) NK cells showing increased expression levels of the transcription factor Hobit...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747084/mir-615-5p-depresses-natural-killer-cells-cytotoxicity-through-repressing-igf-1r-in-hepatocellular-carcinoma-patients
#10
Mai Atef Rahmoon, Rana Ahmed Youness, Asmaa Ibrahim Gomaa, Mohamed Tarif Hamza, Imam Waked, Hend Mohamed El Tayebi, Ahmed Ihab Abdelaziz
miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56(dim), increased CD56(bright) NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins...
July 27, 2017: Growth Factors
https://www.readbyqxmd.com/read/28742190/the-research-on-the-influences-of-hyperthermal-perfusion-chemotherapy-combined-with-immunologic-therapy-on-the-immunologic-function-and-levels-of-circulating-tumor-cells-of-the-advanced-colorectal-cancer-patients-with-liver-metastasis
#11
J-J Sun, G-L Fan, X-G Wang, K Xu
OBJECTIVE: To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. PATIENTS AND METHODS: We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49)...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28733665/human-intrahepatic-cd69%C3%A2-%C3%A2-cd8-t-cells-have-a-tissue-resident-memory-t-cell-phenotype-with-reduced-cytolytic-capacity
#12
Femke Stelma, Annikki de Niet, Marjan J Sinnige, Karel A van Dort, Klaas P J M van Gisbergen, Joanne Verheij, Ester M M van Leeuwen, Neeltje A Kootstra, Hendrik W Reesink
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732877/enhanced-antitumor-activity-of-gemcitabine-by-polysaccharide-induced-nk-cell-activation-and-immune-cytotoxicity-reduction-in-vitro-vivo
#13
Xin Xie, Yiran Zhou, Xue Wang, Jian Guo, Jingwen Li, Hongye Fan, Jie Dou, Baiyong Shen, Changlin Zhou
The polysaccharide SEP has been reported to activate NK and T cells via TLR2/4. Here, the combination of gemcitabine (GEM) and SEP against HepG-2 was investigated. SEP apparently enhanced antitumor activity of gemcitabine against liver cancer through stimulating NKG2D and DAP10/Akt pathway to activate NK cells. The NKG2D upregulation could improve the sensitivity of NK-92 cells targeting to its ligand MICA expressed on HepG-2 cells. Meanwhile, GEM up-regulated MICA expression and attenuated soluble MICA secretion through inhibiting ADAM10 expression, which in turn enhanced the cytotoxicity of NK-92 cells against cancer cells...
October 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28717244/trail-regulatory-receptors-constrain-human-hepatic-stellate-cell-apoptosis
#14
Harsimran D Singh, Itziar Otano, Krista Rombouts, Kasha P Singh, Dimitra Peppa, Upkar S Gill, Katrin Böttcher, Patrick T F Kennedy, Jude Oben, Massimo Pinzani, Henning Walczak, Giuseppe Fusai, William M C Rosenberg, Mala K Maini
The TRAIL pathway can mediate apoptosis of hepatic stellate cells to promote the resolution of liver fibrosis. However, TRAIL has the capacity to bind to regulatory receptors in addition to death-inducing receptors; their differential roles in liver fibrosis have not been investigated. Here we have dissected the contribution of regulatory TRAIL receptors to apoptosis resistance in primary human hepatic stellate cells (hHSC). hHSC isolated from healthy margins of liver resections from different donors expressed variable levels of TRAIL-R2/3/4 (but negligible TRAIL-R1) ex vivo and after activation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710903/stellate-cells-orchestrate-concanavalin-a-induced-acute-liver-damage
#15
Richa Rani, Ashish Tandon, Jiang Wang, Sudhir Kumar, Chandrashekhar R Gandhi
Concanavalin A (ConA) causes immune cell-mediated liver damage, but the contribution of resident nonparenchymal cells is also evident. Hepatic stellate cells (HSCs) induce hepatic inflammation and immunological reactions; we therefore investigated their role in ConA-induced liver injury. ConA was administered i.v. to control or HSC-depleted mice; hepatic histopathology and cytokines/chemokines were determined after 6 hours. In vitro, the effects of ConA-conditioned HSC medium on hepatocytes were determined...
July 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28710878/6-mercaptopurine-modifies-cerebrospinal-fluid-t-cell-abnormalities-in-paediatric-opsoclonus-myoclonus-as-steroid-sparer
#16
M R Pranzatelli, E D Tate, T J Allison
The purpose of this study was to evaluate the capacity of 6-mercaptopurine (6-MP), a known immunosuppressant, to normalize cerebrospinal fluid (CSF) lymphocyte frequencies in opsoclonus-myoclonus syndrome (OMS) and function as a steroid sparer. CSF and blood lymphocytes were immunophenotyped in 11 children with OMS (without CSF B cell expansion) using a comprehensive panel of cell surface adhesion, activation and maturation markers by flow cytometry, and referenced to 18 paediatric controls. Drug metabolites, lymphocyte counts and liver function tests were used clinically to monitoring therapeutic range and toxicity...
July 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28707278/daclizumab-development-clinical-trials-and-practical-aspects-of-use-in-multiple-sclerosis
#17
REVIEW
Laura E Baldassari, John W Rose
Daclizumab is a humanized monoclonal antibody directed towards CD25, the alpha subunit of the high-affinity interleukin (IL)-2 receptor. Daclizumab exerts its effects via multiple mechanisms, including reduction of IL-2-mediated lymphocyte activation and upregulation of CD56-bright natural killer cells. Intravenous daclizumab (Zenapax™) was initially approved for prevention of rejection in renal transplant. In subsequent early testing, followed by larger-scale phase II and phase III trials, both intravenous and subcutaneous daclizumab have demonstrated clinical efficacy in the treatment of multiple sclerosis...
July 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28706073/mouse-models-of-acute-and-chronic-hepacivirus-infection
#18
Eva Billerbeck, Raphael Wolfisberg, Ulrik Fahnøe, Jing W Xiao, Corrine Quirk, Joseph M Luna, John M Cullen, Alex S Hartlage, Luis Chiriboga, Kalpana Ghoshal, W Ian Lipkin, Jens Bukh, Troels K H Scheel, Amit Kapoor, Charles M Rice
An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Whereas immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and associated with liver injury...
July 14, 2017: Science
https://www.readbyqxmd.com/read/28694168/characterizing-porcine-invariant-natural-killer-t-cells-a-comparative-study-with-nk-cells-and-t-cells
#19
Guan Yang, Bianca L Artiaga, Sarah T Lewis, John P Driver
CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells that share phenotypic characteristics of both NK and conventional T cells (Tconv). Although iNKT cells have been well characterized in mice and humans, functional CD1d and CD1d-restricted iNKT cells are not universally expressed in mammals. Swine express iNKT cells that can be detected using α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. In the present study, we characterized iNKT cells from the blood, spleen, lymph node, lung and liver of commercial mixed-breed pigs, and compared their phenotype to NK cells and Tconv...
July 8, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28692048/increased-expression-of-programmed-cell-death-protein-1-on-nk-cells-inhibits-nk-cell-mediated-anti-tumor-function-and-indicates-poor-prognosis-in-digestive-cancers
#20
Y Liu, Y Cheng, Y Xu, Z Wang, X Du, C Li, J Peng, L Gao, X Liang, C Ma
Abnormal expression of activating/inhibitory receptors leads to natural killer (NK) cells dysfunction in tumor. Here we show that programmed cell death protein 1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on peripheral and tumor-infiltrating NK cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. The increased PD-1 expression on NK cells indicates poorer survival in esophageal and liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro...
July 10, 2017: Oncogene
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