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https://www.readbyqxmd.com/read/28100256/transcriptomic-signatures-differentiate-survival-from-fatal-outcomes-in-humans-infected-with-ebola-virus
#1
Xuan Liu, Emily Speranza, César Muñoz-Fontela, Sam Haldenby, Natasha Y Rickett, Isabel Garcia-Dorival, Yongxiang Fang, Yper Hall, Elsa-Gayle Zekeng, Anja Lüdtke, Dong Xia, Romy Kerber, Ralf Krumkamp, Sophie Duraffour, Daouda Sissoko, John Kenny, Nichola Rockliffe, E Diane Williamson, Thomas R Laws, Magassouba N'Faly, David A Matthews, Stephan Günther, Andrew R Cossins, Armand Sprecher, John H Connor, Miles W Carroll, Julian A Hiscox
BACKGROUND: In 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality. RESULTS: The data demonstrate that individuals who succumbed to the disease show stronger upregulation of interferon signalling and acute phase responses compared to survivors during the acute phase of infection...
January 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28095507/choline-deficiency-causes-colonic-type-ii-natural-killer-t-nkt-cell-loss-and-alleviates-murine-colitis-under-type-i-nkt-cell-deficiency
#2
Shintaro Sagami, Yoshitaka Ueno, Shinji Tanaka, Akira Fujita, Hiroaki Niitsu, Ryohei Hayashi, Hideyuki Hyogo, Takao Hinoi, Yasuhiko Kitadai, Kazuaki Chayama
Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet...
2017: PloS One
https://www.readbyqxmd.com/read/28093522/cutting-edge-human-cd49e-nk-cells-are-tissue-resident-in-the-liver
#3
Han Xian Aw Yeang, Sytse J Piersma, Yiing Lin, Liping Yang, Olga N Malkova, Cathrine Miner, Alexander S Krupnick, William C Chapman, Wayne M Yokoyama
Most knowledge on NK cells is based on studies of what are now known as conventional NK cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared with conventional NK cells. In this study, we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e(-) NK cells are tissue resident in the liver...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093337/nk-cell-phenotypic-and-functional-shifts-coincide-with-specific-clinical-phases-in-the-natural-history-of-chronic-hbv-infection
#4
Rik A de Groen, Jun Hou, Gertine W van Oord, Zwier M A Groothuismink, Marieke van der Heide, Robert J de Knegt, André Boonstra
BACKGROUND: Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. METHODS: Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells...
January 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-il-23-mediated-protection-against-cona-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#5
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδT cells and liver damage in patients with HBV. However, whether γδT cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using hepatitis B virus transgenic (HBs-Tg) and HBs-Tg-TCRδ(-/-) mice, we found that mice genetically deficient in γδT cells exhibited more severe liver damage upon ConcanavalinA (ConA) treatment, as indicated by substantially higher serum alanine aminotransferase (ALT) levels, further elevated IFN-γ levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28073411/-effect-of-umbilical-cord-mesenchymal-stem-cell-transplantation-on-immune-function-and-prognosis-of-patients-with-decompensated-hepatitis-b-cirrhosis
#6
X Q Fang, J F Zhang, H Y Song, Z L Chen, J Dong, X Chen, J J Pan, B Liu, C X Chen
Objective: To investigate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on the immune function and prognosis of patients with decompensated hepatitis B cirrhosis. Methods: A total of 65 patients with decompensated hepatitis B cirrhosis were divided into observation group and control group. The patients in the observation group were given intervention (via the proper hepatic artery or the portal vein) and intravenous infusion of 4×10(8) hUCMSCs in two doses, as well as the same basic treatment as in the control group...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28069109/immunomodulatory-effects-of-bone-marrow-mesenchymal-stem-cells-overexpressing-heme-oxygenase-1-protective-effects-on-acute-rejection-following-reduced-size-liver-transplantation-in-a-rat-model
#7
Zhong-Yang Shen, Bin Wu, Tao Liu, Yang Yang, Ming-Li Yin, Wei-Ping Zheng, Bo-Ya Zhang, Hong-Li Song
Here we explore the T-lymphocyte suppressive and immunomodulatory effects of bone marrow mesenchymal stem cells (BMMSCs) overexpressing heme oxygenase-1 (HO-1) on acute rejection following reduced-size liver transplantation (RLT) in a rat model. The proliferation activity, cell cycle progression, secretion of proinflammatory cytokines, expression of CD25 and CD71 in lymphocytes, and activity of NK cells were found to be significantly lowered, and the proportion of regulatory T cells (Tregs) was found to be increased relative to BMMSCs when Adv-HO-1/BMMSCs were co-cultured with Con A ex vivo; secretion of anti-inflammatory cytokines was significantly higher...
December 26, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28067024/treatment-with-alpha-galactosylceramide-protects-mice-from-early-onset-of-non-alcoholic-steatohepatitis-role-of-intestinal-barrier-function
#8
Anna Janina Engstler, Cathrin Sellmann, Cheng Jun Jin, Annette Brandt, Kathleen Herz, Josephine Priebs, Ina Bergheim
SCOPE: The role of invariant natural killer T cells in the development of non-alcoholic steatohepatitis (NASH) has not yet been fully understood. Here, the effect of the invariant natural killer T cell activator alpha-galactosylceramide (αGalCer) on the development of non-alcoholic fatty liver disease and intestinal barrier function was assessed in a mouse model of early Western-style diet (WSD)-induced NASH. METHODS AND RESULTS: Female C57BL/6J mice were either fed a liquid control diet or a liquid fructose-enriched WSD for 6 weeks while being treated 3-times weekly with αGalCer (2 μg i...
January 9, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28065449/a-specific-immune-tolerance-toward-offspring-cells-is-to-exist-after-the-mother-lymphocyte-infusion
#9
Haizhou Xing, Shiqin Liu, Xue Chen, Fang Fang, Xueqiang Wu, Ping Zhu
PURPOSE: To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. METHODS: Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10(7) of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected...
December 26, 2016: Immunobiology
https://www.readbyqxmd.com/read/28058287/impact-of-il-27-on-hepatocyte-antiviral-gene-expression-and-function
#10
Narayan Ramamurthy, Sara Boninsegna, Rebecca Adams, Natasha Sahgal, Helen Lockstone, Dilair Baban, Emanuele Marchi, Paul Klenerman
Background: Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines. It is a potent cytokine, with potential antiviral impact, and has been shown to play a role in modulating functions of diverse cell types, including Th1, Th2, and NK and B cells, demonstrating both pro- and anti-inflammatory roles.  In hepatocytes, it is capable of inducing signal transducer and activator of transcription (STAT)1, STAT3 and interferon-stimulated genes. Methods: To address its role in viral hepatitis, the antiviral activity of IL-27 against hepatitis C virus (HCV) and hepatitis B virus (HBV) was tested in vitro using cell-culture-derived infectious HCV (HCVcc) cell culture system and the HepaRG HBV cell culture model...
November 17, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28045877/the-path-to-cancer-and-back-immune-modulation-during-hepatitis-c-virus-infection-progression-to-fibrosis-and-cancer-and-unexpected-roles-of-new-antivirals
#11
Jose D Debes, Robert J de Knegt, Andre Boonstra
Hepatitis C virus (HCV) infection affects over 130 million individuals worldwide, and it is the number 1 reason for liver transplantation in the United States. HCV infection progresses in a slow chronic fashion eliciting a strong but ineffective immune response, mainly characterized by NK cell dysfunction and T cell exhaustion. The chronic hepatic inflammation leads to liver fibrosis, cirrhosis and cancer in a significant number of patients. In recent years, groundbreaking research has led to the discovery of new HCV-specific direct acting antivirals (DAAs), which have an unprecedented efficacy to clear the virus, and establish a sustained virological response...
December 30, 2016: Transplantation
https://www.readbyqxmd.com/read/28041834/the-hla-g-14-base-pair-deletion-allele-and-the-deletion-deletion-genotype-are-associated-with-persistent-hbe-antigenemia-in-chronic-hepatis-b-infection
#12
Sandro da Costa Ferreira, Silvana Gama Florêncio Chachá, Fernanda Fernandes Souza, Andreza Corrêa Teixeira, Rodrigo de Carvalho Santana, Neifi Hassan Saloun Deghaide, Sandra Rodrigues, Leonardo A Marano, Celso Teixeira Mendes-Junior, Leandra Naira Zambelli Ramalho, Sérgio Zucoloto, Eduardo Antônio Donadi, Ana de Lourdes Candolo Martinelli
BACKGROUND AND AIMS: HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection. METHODS: We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals...
December 29, 2016: Human Immunology
https://www.readbyqxmd.com/read/28031334/respiratory-influenza-virus-infection-induces-memory-like-liver-nk-cells-in-mice
#13
Tingting Li, Jian Wang, Yanshi Wang, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28031333/t-cells-infiltrating-diseased-liver-express-ligands-for-the-nkg2d-stress-surveillance-system
#14
Wei-Chen Huang, Nicholas J Easom, Xin-Zi Tang, Upkar S Gill, Harsimran Singh, Francis Robertson, Chiwen Chang, John Trowsdale, Brian R Davidson, William M Rosenberg, Giuseppe Fusai, Antoine Toubert, Patrick T Kennedy, Dimitra Peppa, Mala K Maini
NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)-specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28018292/obesity-an-immunometabolic-perspective
#15
REVIEW
Indrani Ray, Sushil K Mahata, Rajat K De
Obesity, characterized by chronic activation of inflammatory pathways, is a critical factor contributing to insulin resistance (IR) and type 2 diabetes (T2D). Free fatty acids (FFAs) are increased in obesity and are implicated as proximate causes of IR and induction of inflammatory signaling in adipose, liver, muscle, and pancreas. Cells of the innate immune system produce cytokines, and other factors that affect insulin signaling and result in the development of IR. In the lean state, adipose tissue is populated by adipose tissue macrophage of the anti-inflammatory M2 type (ATM2) and natural killer (NK) cells; this maintains the insulin-sensitive phenotype because ATM2 cells secrete IL10...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27994596/cytoplasm-translocated-ku70-80-complex-sensing-of-hbv-dna-induces-hepatitis-associated-chemokine-secretion
#16
Young Li, Yang Wu, Xiaohu Zheng, Jingjing Cong, Yanyan Liu, Jiabin Li, Rui Sun, Zhigang G Tian, Haiming M Wei
Chronic hepatitis B virus (HBV) infection remains a serious disease, mainly due to its severe pathological consequences, which are difficult to cure using current therapies. When the immune system responds to hepatocytes experiencing rapid HBV replication, effector cells (such as HBV-specific CD8+ T cells, NK cells, NKT cells, and other subtypes of immune cells) infiltrate the liver and cause hepatitis. However, the precise recruitment of these cells remains unclear. In the present study, we found that the cytoplasm-translocated Ku70/80 complex in liver-derived cells sensed cytosolic HBV DNA and promoted hepatitis-associated chemokine secretion...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27980102/blocking-the-ccl2-ccr2-axis-using-ccl2-neutralizing-antibody-is-an-effective-therapy-for-hepatocellular-cancer-in-a-mouse-model
#17
Kun-Yu Teng, Jianfeng Han, Xiaoli Zhang, Shu-Hao Hsu, Shun He, Nissar Wani, Juan Barajas, Linda A Snyder, Wendy L Frankel, Michael A Caligiuri, Samson T Jacob, Jianhua Yu, Kalpana Ghoshal
Hepatocellular carcinoma (HCC), a deadly disease, commonly arises in the setting of chronic inflammation. C-C motif chemokine ligand2 (CCL2/MCP1), a chemokine that recruits CCR2-positive immune cells to promote inflammation, is highly upregulated in HCC patients. Here, we examined the therapeutic efficacy of CCL2-CCR2 axis inhibitors against hepatitis and HCC in the miR-122 knockout (aka KO) mouse model. This mouse model displays upregulation of hepatic CCL2 expression, which correlates with hepatitis that progress to HCC with age...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27956525/il-17c-il-17re-augments-t-cell-function-in-autoimmune-hepatitis
#18
Jinling Huang, Qing Yuan, Hui Zhu, Lan Yin, Shanjuan Hong, Zhongjun Dong, Wei Jin, Chen Dong
Autoimmune hepatitis is a worldwide health problem and significant cause of mortality. However, the disease etiology is largely unknown, which accounts for ineffective treatment and uncontrolled disease progression. In this study, we demonstrated the functional importance of the IL-17C/IL-17RE axis in Con A-induced hepatitis. Elevated IL-17C expression was detected in liver samples of both human and mouse autoimmune hepatitis. IL-17C, produced by hepatocytes, and its specific receptor IL-17RE on liver-resident T cells were both found to be required in Con A-induced liver damage...
December 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27941432/immune-reconstitution-following-hcv-clearance-with-direct-antiviral-agents-potential-consequences-for-patients-with-hcc
#19
Jens M Werner, Akinbami Adenugba, Ulrike Protzer
Recent introduction of all-oral direct acting antiviral treatment has revolutionized care of patients with chronic hepatitis C virus infection. Since patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response...
December 8, 2016: Transplantation
https://www.readbyqxmd.com/read/27940158/inactivation-of-maternal-hif-1%C3%AE-at-mid-pregnancy-causes-placental-defects-and-deficits-in-oxygen-delivery-to-the-fetal-organs-under-hypoxic-stress
#20
Doreswamy Kenchegowda, Bryony Natale, Maria A Lemus, David R Natale, Steven A Fisher
A critical transition occurs near mid-gestation of mammalian pregnancy. Prior to this transition, low concentrations of oxygen (hypoxia) signaling through Hypoxia Inducible Factor (HIF) functions as a morphogen for the placenta and fetal organs. Subsequently, functional coupling of the placenta and fetal cardiovascular system for oxygen (O2) transport is required to support the continued growth and development of the fetus. Here we tested the hypothesis that Hif-1α is required in maternal cells for placental morphogenesis and function...
December 9, 2016: Developmental Biology
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